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Chapter 2: Protein Structure

2.1 Amino mountain Structure and Properties

2.2 Peptide bond Formation and also Primary Protein Structure

2.3 secondary Protein Structure

2.4 Supersecondary Structure and Protein Motifs

2.5 Tertiary and also Quaternary Protein Structure

2.6 Protein Folding, Denaturation and Hydrolysis

2.7 References

2.1 Amino acid Structure and also Properties

Proteins are one of the most abundant organic molecule in living systems and also have the many diverse selection of attributes of every macromolecules. Proteins might be structural, regulatory, contractile, or protective; they might serve in transport, storage, or membranes; or they might be toxin or enzymes. Each cell in a life system may contain thousands of various proteins, each through a distinctive function. Their structures, like their functions, differ greatly. They are all, however, polymers that alpha amino acids, arranged in a direct sequence and connected with each other by covalent bonds.

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Alpha Amino acid Structure

The significant building block of proteins are dubbed alpha (α) amino acids. Together their name indicates they save on computer a carboxylic acid sensible group and also an amine useful group. The alpha designation is used to indicate that these two functional groups are separated indigenous one one more by one carbon group. In addition to the amine and the carboxylic acid, the alpha carbon is additionally attached come a hydrogen and one added group that deserve to vary in size and also length. In the diagram below, this group is designated together an R-group. Within living biology there space 20 amino acids offered as protein building blocks. They differ from one one more only in ~ the R-group position. The an easy structure of one amino mountain is shown below:


Figure 2.1 basic Structure of an Alpha Amino Acid

There are a full of 20 alpha amino acids that are typically incorporated right into protein structures (Figure 2.x). The different R-groups have different characteristics based on the nature that atoms integrated into the useful groups. There room R-groups that mainly contain carbon and also hydrogen and also are an extremely nonpolar or hydrophobic. Rather contain polar uncharged functional teams such together alcohols, amides, and also thiols. A couple of amino mountain are simple (containing amine functional groups) or acidic (containing carboxylic acid useful groups). This amino acids are capable of developing full charges and also can have actually ionic interactions. Every amino acid have the right to be abbreviated making use of a 3 letter and a one letter code.



Figure 2.2 framework of the 20 Alpha Amino Acids used in Protein Synthesis. R-groups are shown by circled/colored portion of each molecule. Color indicate particular amino mountain classes: Hydrophobic – Green and also Yellow, Hydrophilic Polar Uncharged – Orange, Hydrophilic Acidic – Blue, Hydrophilic basic – Rose.

Click here for a Downloadable variation of the Amino acid Chart

Nonpolar (Hydrophobic) Amino Acids

The nonpolar amino acids can largely it is in subdivided right into two more specific classes, the aliphatic amino acids and the aromatic amino acids. The aliphatic amino mountain (glycine, alanine, valine, leucine, isoleucine, and proline) generally contain branched hydrocarbon chains v the most basic being glycine to the more complicated structures that leucine and valine. Proline is additionally classified together an aliphatic amino acid yet contains unique properties together the hydrocarbon chain has actually cyclized through the terminal amine producing a unique 5-membered ring structure. As we will view in the next section covering main structure, proline deserve to significantly alter the 3-dimentional structure of the due to the structure rigidity of the ring structure as soon as it is incorporated into the polypeptide chain and is typically found in regions of the protein wherein folds or transforms occur.

The aromatic amino acids (phenylalanine, tyrosine, and also tryptophan), as their surname implies, contain an fragrant functional groups within their structure making them greatly nonpolar and hydrophobic due to the high carbon/hydrogen content. However, it need to be provided that hydrophobicity and also hydrophilicity represent a slide scale and each of the different amino acids can have different physical and also chemical properties relying on their structure. For example, the hydroxyl group present in tyrosine boost its reactivity and also solubility contrasted to the of phenylalanine.

Methionine, one of the sulfur-containing amino acids is typically classified under the nonpolar, hydrophobic amino acids together the terminal methyl team creates a thioether functional group which generally cannot type a permanent dipole within the molecule and retains short solubility.

Polar (Hydrophilic) Amino Acids

The polar, hydrophilic amino acids deserve to be subdivided into three significant classes, the polar uncharged-, the acidic-, and the basic- practical groups. In ~ the polar uncharged class, the side chains save heteroatoms (O, S, or N) that are qualified of creating permanent dipoles within the R-group. These incorporate the hydroxyl- and also sulfoxyl-containing amino acids, serine, threonine, and cysteine, and the amide-containing amino acids, glutamine and asparigine. Two amino acids, glutamic acid (glutamate), and also aspartic mountain (aspartate) constitute the acidic amino acids and contain next chains through carboxylic acid practical groups qualified of completely ionizing in solution. The basic amino acids, lysine, arginine, and histidine contain amine functional teams that have the right to be protonated to carry a full charge.

Many of the amino acids with hydrophilic R-groups deserve to participate in ~ the active site that enzymes. An active site is the component of one enzyme that directly binds come a substrate and carries a reaction. Protein-derived enzyme contain catalytic groups consist of of amino mountain R-groups that promote formation and degradation of bonds. The amino acids the play a far-reaching role in the binding specificity of the active site space usually not adjacent to each other in the primary structure, but form the active site as a result of urgent in producing the tertiary structure, as you will see later in the chapter.

Protein structures constructed from the an easy amino acids have the right to be numerous amino mountain long. Thus, for simplicity sake, the 20 amino acids offered for protein synthesis have both three letter and one letter password abbreviations (Table 2.1). These abbreviations are commonly used come delineate protein sequences for bioinformatic and research purposes.

Table 2.1 α-Amino mountain Abbreviations


Thought Question: Tryptophan contains an amine sensible group, why isn’t tryptophan basic?

Answer: Tryptophan includes an indole ring framework that contains the amine functional group. However, due to the proximity of, and electron withdrawing nature that the aromatic ring structure, the lone pair of electrons on the nitrogen space unavailable to accept a proton. Rather they are associated in forming pi-bonds within numerous of the different resonance structures feasible for the indole ring. Number 2.3A shows 4 of the possible resonance structures for indole. Conversely, in ~ the immidazole ring structure uncovered in histidine, there are two nitrogen atoms, one of which is involved in the development of resonance structures (Nitrogen #1 in number 2.3B) and also cannot accept a proton, and the various other (Nitrogen #3) that has a lone pair of electrons that is available to accept a proton.


Figure 2.3 to compare of the Structural ease of access of Lone Pair of electrons on Nitrogen to accept a Proton in the Indole and also Immidizole Ring Structures. (A) displayed are 4 resonance structures of the indole ring framework demonstrating that the lone pair of electrons on the nitrogen are involved in the formation of pi-bonds. (B) The immidazole ring structure has one nitrogen (1) that is connected in resonance structures (not shown) and also is not obtainable to accept a proton, while the 2nd nitrogen (3) has a lone pair that electrons accessible to accept a proton together shown.

Work It out on her Own:

Given the example above, define using a chemical diagram, why the amide nitrogen atoms found in asparagine and glutamine are not basic.

Alpha Amino Acids room Chiral Molecules

If you examine the structure of the alpha carbon within each of the amino acids, girlfriend will notice that all of the amino acids, except for glycine are chiral molecules (Figure 2.4) A chiral molecule is one the is not superimposable v its mirror image. Like left and also right hand that have a thumb, fingers in the very same order, but are winter images and not the same, chiral molecules have the very same things enclosed in the exact same order, but are winter images and not the same. The mirror picture versions that chiral molecules have physical properties the are virtually identical come one another, making it very an overwhelming to phone call them except one one more or come separate. Therefore nature, lock are provided a special stereoisomer name dubbed enantiomers and in fact, the compounds themselves are given the very same name! these molecules carry out differ in the way that lock rotate plain polarized light and the method that they reaction with and interact with biological molecules. Molecule that turn the light in the right-handed direction are referred to as dextrorotary and also are provided a D- letter designation. Molecules that revolve light in the left-handed direction are referred to as levorotary and are provide an L- letter designation to distinguish one enantiomer native the other. The D- and also L- creates of alanine are present in figure 2.4B.

Although many amino acids have the right to exist in both left and also right handed forms, life on planet is make of left handed amino acids, virtually exclusively. Proteogenic amino acids integrated into proteins by ribosome are always in the L-conformation. Part bacteria have the right to incorporate D-amino acids right into non-ribosomally encoded peptides, but the usage of D-amino mountain in nature is rare. Interestingly, when we will comment on the structure of sugars in chapter XX, us will discover that sugars the are included into carbohydrate structures are practically exclusively in the D-conformation. No one knows why this is the case. However, Drs. Man Cronin and Sandra Pizzarello have displayed that the the amino acids that fall to earth from space on meteorites, an ext are in the L-conformation 보다 the D-conformation. Thus, the fact that we space made mostly of L-amino acids might be since of amino mountain from space.

Why carry out amino mountain in an are favor the L-conformation? No one really knows, yet it is well-known that radiation can additionally exist in left and right handed forms. So, over there is a theory called the Bonner hypothesis, the proposes the the predominant forms of radiation in room (ie. From a rotating neutron star for example) can lead come the selective formation of homochiral molecules, such as L-amino acids and D-sugars. This is still speculative, however recent result from meteorites make this hypothesis much much more plausible.


Figure 2.4 Amino acid Chirality. Except for the most basic amino acid, glycine, all of the other amino acids the are included into protein structures space chiral in nature. (A) demonstrates the chirality that the core alpha amino acid structure when the non-specific R-group is used. (B) The D- and L-Alanine enantiomer pair, upper diagram to represent the ball and stick model and the reduced diagram to represent the heat structure.

Image (A) native NASA

Note that the D- and also L-designations are details terms offered for the method a molecule rotates plain polarized light. It does not represent the absolute stereo configuration the a molecule. One absolute configuration refers to the spatial arrangement of the atoms of a chiral molecular reality (or group) and its stereochemical summary e.g. R or S, referring to Rectus, or Sinister, respectively.

Absolute configurations because that a chiral molecule (in pure form) are most often obtained by X-ray crystallography. Different techniques room optical rotatory dispersion, vibrational circular dichroism, use of chiral change reagents in proton NMR and Coulomb to explode imaging. As soon as the pure configuration is derived the assignment that R or S is based on the Cahn–Ingold–Prelog priority rules, which deserve to be the evaluation by complying with the link and in figure 2.5. All of the chiral amino acids, except for cysteine, are additionally in the S-conformation. Cysteine, includes the sulfur atom leading to the R-group to have higher priority than the carboxylic acid useful group, leading to the R-conformation because that the pure stereochemistry. However, cysteine walk rotate level polarized light in the levorotary or left-handed direction. Thus, the R- and also S-designations perform not constantly correspond v the D- and L- conformation.


Figure 2.5 pure Configuration is identified by the Rectus (R) and Sinister (S) Designations. In the Cahn Ingold Prelog device for naming chiral centers, the groups attached to the chiral facility are ranked according to their atomic number v the highest possible atomic number receiving the highest possible priority (A in the chart above) and the shortest atomic number receiving the lowest priority (D in the chart above). The shortest priority is climate pointed far from the viewer to correctly orient the molecule for more evaluation. The route of top priorities #1, #2, and also #3 (corresponding to A, B and also C above) space then traced. If the path is is in the clockwise direction, the chiral center is offered the R-designation, vice versa, if the route is counterclockwise, the is provided the S-designation.

Image from CC BY-SA 3.0, Link">Wikipedia

Amino Acids are Zwitterions

In chemistry, a zwitterion is a molecule v two or an ext functional groups, of i beg your pardon at least one has actually a positive and one has a an adverse electrical charge and also the net fee of the entire molecule is zero at a certain pH. Because they save at least one positive and also one negative charge, zwitterions are likewise sometimes dubbed inner salts. The charges on the different functional groups balance each other out, and the molecule together a entirety can it is in electrically neutral in ~ a details pH. The pH where this wake up is recognized as the isoelectric point.

Unlike an easy amphoteric link that may only form either a cationic or anionic species, a zwitterion simultaneously has both ionic states. Amino mountain are examples of zwitterions (Figure 2.6). These compounds save an ammonium and a carboxylate group, and can be regarded as occurring via a kind of intramolecular acid–base reaction: The amine team deprotonates the carboxylic acid.


Figure 2.6 Amino Acids room Zwitterions. An amino acid consists of both acidic (carboxylic acid fragment) and basic (amine fragment) centres. The isomer ~ above the right is the zwitterionic form.

Because amino acids are zwitterions, and also several also contain the potential because that ionization within your R-groups, their charge state in vivo, and also thus, your reactivity deserve to vary relying on the pH, temperature, and solvation condition of the local microenvironment in i beg your pardon they space located. The graph of typical pKa worths for the amino acids is presented in Table 2.1 and can be used to guess the ionization/charge condition of amino acids and their resulting peptides/proteins. However, it should be provided that the solvation condition in the microenvironment of one amino mountain can change the loved one pKa worths of these functional groups and carry out unique reactive properties in ~ the active sites of enzymes (Table 2.1). A much more in depth conversation of the impacts of desolvation will certainly be given in chapter XX pointing out enzyme reaction mechanisms.

Table 2.1


Printable version of pKa Values

As seen in Table 2.1, seven of the amino mountain contain R-groups with ionizable next chains and also are typically found in the energetic sites that enzymes. Recall the the pKa is defined as the pH at which the ionized and unionized creates of an ionizable functional group within a molecule exist in equal concentrations. Thus, as a functional group shifts over or below its pKa value, there will certainly be a change in the concentration of the ionized and unionized develops favoring one state over the other. Number 2.7 shows the miscellaneous R-groups in their unionized and also ionized states and also their favored states either above or listed below the pKa value.


Figure 2.7 Ionizable Functional groups in typical Amino Acids. Within all amino mountain both the carboxylic acid functional group (C-terminus), and the amine functional team (N-terminus) are qualified of ionization. In addition, 7 amino acids (aspartic acid, glutamic acid, arginine, histidine, lysine, tyrosine, and cysteine) additionally contain ionizable functional teams within their R-groups. The practical group’s favored claims are shown either over or below their corresponding pKa values.

Typically an ionizable group will favor the protonated state in pH conditions below its corresponding pKa values and also will favor the deprotonated state in pH conditions over its particular pKa value. Thus, pKa values can be provided to help predict the overall charge says of amino acids and also their resulting peptides/proteins within a defined environment. For example, if us look in ~ a titration curve because that the simple amino acid, histidine (Figure 2.8). As each pKa is reached, the charge state the the amino mountain is altered to donate the deprotonated state. Thus, histidine will gradually progress native an all at once +2 fee at very low pH (fully protonated) come an all at once -1 charge at really high pH (fully deprotonated).


Figure 2.8 Ionization State of Histidine in different pH Environments. (A) Titration curve of histidine from short pH to high pH. Each equivalence point (pKa) is indicated. (B) mirrors the favored ionization state that histidine adhering to the i of every pKa value.

Image adapted from L. Valve Warren

Extra Practice:

Draw glutamic acid and also predict the all at once charge state of the amino mountain at pH = 1, pH = 3, pH = 7, and pH = 12.

Cysteine and Disulfide bond Formation

Cysteine is likewise a distinctive amino acid as this side chain is qualified of undergoing a reversible oxidation-reduction (redox) reaction with other cysteine residues creating a covalent disulfide shortcut in the oxidized state (Figure 2.9). Remind that as soon as molecules end up being oxidized that they are losing electrons and that once molecules are decreased that castle are acquiring electrons. During organic redox reactions, hydrogen ion (protons) are often removed with the electrons from the molecule throughout oxidation, and are returned throughout reduction. Thus, if a reaction is shedding or obtaining protons, this is a great indication the it is additionally losing or obtaining electrons and also that a oxidization reaction is occurring. Thus, proton gain or loss have the right to be one easy means to determine this reaction type.

Disulfide bonds are integral in the development of the 3-dimentional structure of proteins and also can therefore highly influence the duty of the result protein. In cellular systems, disulfide bond formation/disruption is an enzyme-mediated reaction and can be made use of as a system to control the task of protein. De defiders bonds will be discussed in further information section 2.xx within this chapter and in thing XX.


Figure 2.9 Cysteine can be Oxidized to create Disulfide Bonds. throughout disulfide bond formation, two cysteines are oxidized to type a cystine molecule. This requires the ns of two protons and also two electrons.

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2.2 Peptide bond Formation and Primary Protein Structure

Within to move systems, protein are linked together by a huge enzyme complex that has a mixture of RNA and proteins. This complicated is referred to as the ribosome. Thus, together the amino acids are linked together to kind a certain protein, they are placed within a very specific order the is dictated by the genetic information contained within the messenger RNA (mRNA) molecule. This certain ordering of amino mountain is well-known as the protein’s major sequence. The translation system used through the ribosome to synthesize proteins will certainly be debated in detail in thing XX. This chapter will focus only on the chemical reaction developing during synthesis and also the physics properties that the resulting peptides/proteins.

The major sequence that a protein is connected together utilizing dehydration synthesis (loss the water) that incorporate the carboxylic acid of the upstream amino acid with the amine functional group of the downstream amino acid to form an amide linkage (Figure 2.10). Similarly, the reverse reaction is hydrolysis and also requires the organization of a water molecule to different two amino acids and also break the amide bond. Notably, the ribosome serves as the enzyme that mediates the dehydration synthesis reactions compelled to build protein molecules, conversely, a class of enzymes referred to as proteases are forced for protein hydrolysis.

Within protein structures, the amide linkage in between amino mountain is recognized as the peptide bond. Succeeding amino acids will certainly be added onto the carboxylic acid terminal that the cultivation protein. Thus, protein are constantly synthesized in a directional manner beginning with the amine and also ending with the carboxylic mountain tail. New amino acids room always included onto the carboxylic acid tail, never ever onto the amine that the first amino mountain in the chain. The directionality of protein synthetic is dictated through the ribosome and is well-known as N- to C- synthesis.


Figure 2.10 development of the Peptide Bond. The enhancement of 2 amino acids to form a peptide requires dehydration synthesis.

As detailed above in the zwitterion section, amide bonds have actually a resonance framework that will certainly not permit the nitrogen lone pair of electron to act as a basic (Figure 2.11).


Figure 2.11 Amide Resonance Structure. throughout amide resonance, the lone pair electrons from the nitrogen are affiliated in pi-bond formation with the carbonyl carbon creating the twin bond. Thus, amide nitrogens are not basic. In addition, the C-N bond in ~ the amide structure is addressed in space and cannot rotate as result of the pi-bond character.

Image native V.K. Chang

Instead, castle are involved in pi-bond formation with the carbonyl carbon. Furthermore, the C-N bond in ~ the amide structure is fixed in room and can not rotate due to the pi-bond character. This creates fixed physical locations of the R-groups within the cultivation peptide in either the cis or trans conformations. Since the R-groups deserve to be fairly bulky, lock usually alternative on either next of the farming protein chain in the trans conformation. The cis conformation is only preferred with one particular amino acid, proline. This is due to the cyclic structure of the proline R-group and the steric hindrance the is produced when proline through the trans construction (Figure 2.12). Thus, proline residues deserve to have a huge impact top top the 3-D framework of the resulting peptide.


Figure 2.12 Cis and Trans conformation of Amino acid R-Groups. The upper diagram displays the cis and trans conformations the two surrounding amino acids noted as X and Y i m sorry indicate any of the 20 amino acids, except for proline. In the trans construction the R-group native amino mountain X is rotated away and also on the various other side the the molecule when compared with the R-group native amino acid Y. This conformation provides the least amount that steric hindrance contrasted with the cis conformation where the R-groups are located on the very same side and also in nearby proximity to one another. In the lower diagram, any kind of amino acid, X is positioned upstream that a proline residue. Because of the cyclization that the proline R-group with the amide nitrogen in the backbone, this shifts the position of the proline R-group to be in closer proximity come the R-group native amino acid X when it through the trans conformation. Thus, proline favors the cis construction which has less steric hindrance.

Proteins are very large molecules containing numerous amino mountain residues connected together in very specific order. Proteins variety in size from 50 amino acids in size to the largest recognized protein comprise 33,423 amino acids. Macromolecules through fewer 보다 50 amino acids are well-known as peptides (Figure 2.13).


Figure 2.13 Peptides and also Proteins are macromolecules built from long chains that amino mountain joined together through amide linkages. The order and nature that amino acids in the major sequence that a protein determine the folding pattern of the protein based on the surrounding atmosphere of the protein (ie if that is within the cell, the is most likely surrounded by water in a an extremely polar environment, whereas if the protein is embedded in the plasma membrane, it will be surrounded by an extremely nonpolar hydrocarbon tails).

Due to the big pool that amino acids that have the right to be included at each position within the protein, there room billions the different feasible protein combinations that can be provided to produce novel protein structures! because that example, think about a tripeptide made from this amino mountain pool. In ~ each place there room 20 different alternatives that can be incorporated. Thus, the total variety of resulting tripeptides possible naipublishers.comld be 20 X 20 X 20 or 203, which equates to 8,000 different tripeptide options! currently think around how many alternatives there naipublishers.comld be because that a tiny peptide comprise 40 amino acids. There naipublishers.comld certainly be 2040 options, or a psychic boggling 1.09 X 1052 potential succession options! each of these options naipublishers.comld differ in the all at once protein shape, together the nature of the amino mountain side chains helps to identify the communication of the protein with the other residues in the protein itself and also with its surrounding environment.

The character of the amino acids throughout the protein aid the protein to wrinkles and form its 3-dimentional structure. The is this 3-D shape that is forced for the functional task of the protein (ie. protein shape = protein function). Because that proteins found inside the watery environments of the cell, hydrophobic amino acids will frequently be uncovered on the within of the protein structure, vice versa, water-loving hydrophilic amino acids will certainly be ~ above the surface ar where they deserve to hydrogen bond and also interact v the water molecules. Proline is unique due to the fact that it has actually the only R-group that develops a cyclic framework with the amine functional team in the main chain. This cyclization is what reasons proline to take on the cis conformation fairly than the trans conformation in ~ the backbone. This change is framework will regularly mean the prolines are positions whereby bends or directional transforms occur in ~ the protein. Methionine is unique, in that it serves together the beginning amino acid for almost all of the numerous thousands the proteins well-known in nature. Cysteine contain thiol functional groups and also thus, can be oxidized with various other cysteine residual water to type covalent de defiders bonds within the protein framework (Figure 2.14). De defiders bridges add additional stability to the 3-D structure and are often required for exactly protein folding and duty (Figure 2.14).


Figure 2.14 de defiders Bonds.  de defiders bonds space formed in between two cysteine residues within a peptide or protein sequence or between different peptide or protein chains. In the example over the two peptide chain that form the hormone insulin are depicted. De defiders bridges in between the 2 chains are compelled for the proper function of this hormone to manage blood glucose levels.

Image by: CNX OpenStax via Wikimedia Commons

Protein Shape and also Function

The major structure of each protein leads to the distinct folding pattern that is characteristic for that certain protein. In summary, the major sequence is the straight order of the amino acids as they are connected together in the protein chain (Figure 2.15). In the following section, us will comment on protein urgently that provides rise to secondary, tertiary and also sometimes quaternary protein structures.


Figure 2.15 major protein structure is the direct sequence the amino acids. 

(credit: alteration of occupational by National human Genome research study Institute)

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2.3 second Protein Structure

In the vault section, we noted the rigidity produced by the C-N bond in the amide link when amino acids are joined v one another and also learned that this reasons the amino mountain R-groups to favor the trans confromation (except for proline i beg your pardon favors the cis conformation). This rigidity v the protein backbone limits the urgent potential and patterns of the resulting protein. However, the bonds attached to the α-carbon can freely rotate and contribute to the flexibility and unique folding patterns seen in ~ proteins. To evaluate the possible rotation trends that have the right to arise around the α-carbon, the torsion angles Phi (Φ) and Psi (ψ) are generally measured. The torsion edge Phi (Φ) steps the rotation roughly the α-carbon – nitrogen bond by analyzing the angle between the two neighboring carbonyl carbons when you are looking straight down the α-carbon – nitrogen bond right into the plane of the document (Figure 2.16). Whereas the torsion angle Psi (ψ) measures the rotation roughly the α-carbon – carbonyl carbon bond by examining the angle in between the two surrounding nitrogen atoms as soon as you space looking straight down the α-carbon – carbonyl carbon shortcut (Figure 2.16).


Figure 2.16 Phi (Φ) and Psi (ψ) Torsion Angles. (A) The Phi (Φ) torsion angle is a measure up of the rotation approximately the bond in between the α-carbon and the amide nitrogen. That is measured as the angle between the two carbonyl carbon atoms surrounding to the bond, displayed in the reduced panel. (B) The Psi (ψ) torsion edge is a measure of the rotation around the bond between the α-carbon and the carbonyl carbon. The is measured together the angle between the 2 nitrogen atoms surrounding to the bond, shown in the lower panel.

While the bonds roughly the α-carbon deserve to rotate freely, the favored torsion angle are restricted to a smaller subset that possibilities as bordering atoms prevent conformations that have actually high steric hindrance associated with them. G.N. Ramachandran created computer system models of little peptides to recognize the stable conformations that the Phi (Φ) and Psi (ψ) torsion angles. Through his results, he produced what is known as the Ramachandran Plot, i m sorry graphically displays the overlap regions of the many favorable Phi (Φ) and also Psi (ψ) torsion angle (Figure 2.17)


Figure 2.17 The Ramachandran Plot. Favorable and also highly favorable Phi (Φ) and also Psi (ψ) torsion angle are shown in yellow and red, respectively. Bond angle for common an additional protein structures room indicated.

Image modified from: J. Cooper

Within every protein small regions of the protein may take on specific, repeating urgently patterns. These details motifs or trends are referred to as secondary structure. Two of the many common second structural features encompass alpha helix and beta-pleated sheet (Figure 2.18). Within these structures, intramolecular interactions, specifically hydrogen bonding between the backbone amine and carbonyl functional groups are vital to keep 3-dimensional shape.


Figure 2.18 secondary Structural features in Protein Structure.  The right-handed alpha helix and also beta-pleated sheet are typical structural motifs found in most proteins. Lock are held together by hydrogen bonding in between the amine and also the carbonyl oxygen in ~ the amino acid backbone.

Image modification from: The college of Biomedical scientific researches Wiki

The Alpha Helix

For the alpha helical structures, the right-handed helix is an extremely common, conversely, left-handed helices are very rare. This is because of the Phi (Φ) and Psi (ψ) torsion angles compelled to obtain the left-handed alpha helical structure. The protein naipublishers.comld have to fold and also twist through countless unfavorable angles before obtaining the correct orientation for the left-handed helix. Thus, they are not an extremely common in nature.

For the right-handed alpha helix, every helical turn has 3.6 amino mountain residues (Figure 2.19). The R teams (the variant groups) of the polypeptide protrude out from the α-helix chain. The polypeptide backbone develops a repeating helical framework that is stabilized by hydrogen bonds between a carbonyl oxygen and an amine hydrogen. This hydrogen bonds happen at consistent intervals the one hydrogen link every 4th amino acid and cause the polypeptide backbone to type a helix. Each amino acid advances the helix, along its axis, through 1.5 Å. Each rotate of the helix is created of 3.6 amino acids; thus the key of the helix is 5.4 Å. There is an mean of ten amino mountain residues per helix. Different amino mountain have various propensities for developing α-helix. Amino acids that favor to embrace helical conformations in proteins encompass methionine, alanine, leucine, glutamate and lysine. Proline and glycine have almost no tendency to kind helices.


Figure 2.19 structure of the Right-handed Alpha Helix. (A) Ball and Stick model Side View. A full of 3.6 amino mountain are required to type one rotate of an α-helix. Hydrogen bonding in between the carbonyl oxygen and the nitrogen of the 4th amino acid stabilize the helical structure. Top top the structure shown, the black color atoms room the alpha carbon, grey are carbonyl carbons, red space oxygen, blue are nitrogen, green are R-groups, and light purple room hydrogen atoms. (B) expanded Side View linear Structure and Space-Filling version (C) increased Top View straight Structure and also Space-Filling Model

Image A modified from: Maksim image B and also C from: Henry Jakubowski

Key Points around the Alpha Helix:The alpha helix is more compact than the totally extended polypeptide chain with phi/psi angle of 180oIn proteins, the average number of amino mountain in a helix is 11, which offers 3 turns.The left-handed alpha helix, although permitted from inspections the a Ramachandran plot, is seldom observed, because the amino acids supplied to build protein structure space L-amino acids and are biased towards creating the right-handed helix. When left-handed helices carry out form, they space often an important for the correct protein folding, protein stability, or are directly involved in the development of the active site.


Figure 2.20 Left Handed Alpha Helix Structure. In this diagram the left handed alpha helix, displayed in yellow, is part of a hairpin rotate within the protein structure and also is stabilized by 2 disulfide bridges presented in yellow.

Figure from: Annavarapu, S., Nanda, V. (2009) BMC Struct Biol 9, 61

The core of the helix is pack tightly. There space not holes or pores in the helix.All the R-groups prolong outward and away indigenous the helix axis. The R-groups deserve to be hydrophilic or hydrophobic, and can it is in localized in certain positions top top the helix forming amphipathic regions on the protein or totally hydrophobic helices may additionally extend through the plasma membrane as displayed in number 2.21


Figure 2.21 placing of the R-Groups within Alpha Helical Structures. R-groups might be positioned within the alpha helix to develop amphipathic regions within the protein, wherein hydrophilic residues space positioned on one-side that the helix and also hydrophobic top top the other as shown in the side watch (A) or peak down views (B & C). R-groups may also be fully hydrophobic within alpha helices that expectations the plasma membrane as shown in (D).

Figure modification from: Khara, J.S., et al. (2017) Acta Biomat 57:103-114 and also Ryu, H., et al. (2019) Int J Mol Sci 20 (6) 1437

Some amino mountain are an ext commonly discovered in alpha helices than other. Below are the amino acids the are typically NOT found in alpha helical structures: Gly is too tiny and conformationally versatile to be discovered with high frequency in alpha helices, if Pro is also rigid and in the cis-conformation. Pro often disrupts helical framework by leading to bends in the protein. Part amino acids with side chain that deserve to H-bond (Ser, Asp, and also Asn) and also aren’t also long appear to plot as competitors of key chain H link donor and acceptors, and also destabilize alpha helices. Early on branching R-groups, such together Val and Ile, destabilize the alpha helix as result of steric interactions of the bulky next chains v the helix backbone. Alpha keratins, the significant component of hair, skin, fur, beaks, and also fingernails, are virtually all alpha helix.

Jmol: updated An diverted helix native an Antifreeze Protein Jmol14 (Java) | JSMol (HTML5)

The Beta Pleated Sheet:

In the β-pleated sheet, the “pleats” are formed by hydrogen bonding in between atoms top top the backbone that the polypeptide chain. The R teams are attached to the carbons and also extend over and below the folds of the pleat in the trans conformation. The pleated segments align parallel or antiparallel to each other, and also hydrogen bonds kind between the partially positive nitrogen atom in the amino group and also the partially an adverse oxygen atom in the carbonyl team of the peptide backbone (Figure 2.21).


Figure 2.21 Beta-Pleated paper Structure. The β-pleated sheet have the right to be oriented in the parallel or antiparallel orientation, presented in (A) above with the β-pleated sheet stood for by the red ribbon arrows. The direction of the arrowhead indicated the orientation the the protein through the arrowhead running in the N- to C- direction. Hydrogen bonding in between the backbone carbonyl and the backbone amine functional teams stabilized both the antiparallel (B left) and also the parallel (B right) β-pleated sheet structures.

Image (A) from: Xenoblast Image (B) from: Fvasconcellos

Other second Structure Motifs:

Other important second structures include turns, loops, hairpins and flexible linkers. Over there are many different share of turns within protein structure, including α-turns, β-turns, γ-turns, δ-turns and also π-turns. β-turns (the most typical form) generally contain 4 amino mountain residues (Fig 2.22). Proline and also Glycine are frequently found in turn motifs, as the cis conformation of Proline favors cheater conformational bends, if the minimal Glycine side chain permits for tighter pack of the amino mountain to favor the revolve structure.


Figure 2.22 Schematic of type I and II β-turns.

Image from: Muskid

An ω-loop is a catch-all term because that a longer, extended or rarely often, rarely loop without fixed interior hydrogen bonding. A hairpin is a special situation of a turn, in which the direction that the protein backbone reverses and also the flanking second structure elements interact. For example, a beta hairpin connects two hydrogen-bonded, antiparallel β-strands. Turns are sometimes uncovered within functional linkers or loops connecting protein domains. Linker sequences differ in length and are typically rich in polar uncharged amino acids. Flexible linkers allow connecting domain names to freely twist and rotate to recruit your binding partner via protein domain dynamics.

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2.4 Supersecondary Structure and also Protein Motifs

In in between the secondary structure and also tertiary framework of protein are bigger 3-dimensional features that have been figured out in multiple different protein structures. Castle are recognized as supersecondary structure and also as protein motifs. Supersecondary structure is commonly composed that two second structures connected together by a turn and includes helix-turn-helix, helix-loop-helix, α-α corners, β-β corners, and β-hairpin-β (Figure 2.23). 


Figure 2.23 instances of Supersecondary Structures. (A) β-hairpin-β frameworks are characterized by a sharp hairpin rotate that does not disrupt the hydrogen bonding of the 2 β-pleated paper structures. (B) suggest helix-turn-helix framework of the Taspase1 protein, (C) α-α corner structure current in the Myoglobin protein.

Image A by: Isabella Daidone photo B by: johannes van den Boom, et al. (2016) PLosONE 11(3):e0151431

Image C modification from: Belles14104

Protein motifs are more complicated structures developed from secondary and supersecondary structural materials that are repetitive modalities visualized in many protein structures.

Beta strands have a tendency to twisted in the best hand direction to aid minimize conformational energy. This leader to the formation of interesting structural motifs uncovered in many varieties of proteins. 2 of this structures encompass twisted sheets or saddles and beta barrels (Figure 2.24)


Figure 2.24 typical Beta Strand structural Motifs. (A) Right-handed Twisted sheet Top and also Side View, (B) Beta Barrel side View, and (C) Beta Barrel height View

Image by: Henry Jakubowski

Structural motifs deserve to serve particular functions within proteins together as permitting the binding the substrates or cofactors. For example, the Rossmann wrinkles is responsible for binding to nucleotide cofactors such together nicotinamide adenine dinucleotide (NAD+) (Figure 2.25). The Rossmann wrinkles is composed of six parallel beta strands that type an expanded beta sheet. The very first three strands are associated by α-helices leading to a beta-alpha-beta-alpha-beta structure. This pattern is replicated once to develop an turning back tandem repeat containing 6 strands. Overall, the strands room arranged in the bespeak of 321456 (1 = N-terminal, 6 = C-terminal). 5 stranded Rossmann-like folds are arranged in the stimulate 32145. The in its entirety tertiary structure of the wrinkles resembles a three-layered sandwich within the filling is written of an extensive beta sheet and the 2 slices that bread are created by the connecting parallel alpha helices.


Figure 2.25 The Rossman Fold.  (A) structure of Nicotinamide Adenine dinucleotide (NAD+) (B) Cartoon diagram of the Rossmann fold (helices A-F red and also strands 1-6 yellow) indigenous E. Coli malate dehydrogenase enzyme. The NAD+ cofactor is shown binding together the space filling molecule. (C) Schematic diagram of the 6 stranded Rossmann fold.

Image modification from: Boghog

One the the attributes if the Rossmann wrinkles is the co-factor binding specificity. The most conserved segment that Rossmann wrinkle is the very first beta-alpha-beta segment. Due to the fact that this segment is in contact with the ADP portion of dinucleotides such together FAD, NAD and NADP the is additionally called together an “ADP-binding beta-beta fold”.

Interestingly, similar structural motifs do not always have a typical evolutionary ancestor and also can arise by convergent evolution. This is the case with the TIM Barrel, a conserved protein fold consisting the eight α-helices and eight parallel β-strands that alternating along the peptide backbone. The structure is named after triosephosphate isomerase, a conserved metabolic enzyme. TIM barrels are among the most common protein folds. Among the many intriguing features amongst members of this course of proteins is back they every exhibit the same tertiary fold there is very little sequence similarity between them. At the very least 15 distinctive enzyme family members use this framework to generate the appropriate active site geometry, always at the C-terminal finish of the eight parallel beta-strands of the barrel.

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Figure 2.26 The TIM Barrel. TIM barrels are thought about α/β protein folds due to the fact that they incorporate an alternate pattern of α-helices and β-strands in a single domain. In a TIM barrel the helices and strands (usually 8 of each) form a solenoid the curves about to nearby on itself in a doughnut shape, topologically well-known as a toroid. The parallel β-strands type the inner wall surface of the doughnut (hence, a β-barrel), vice versa, the α-helices type the outer wall of the doughnut. Each β-strand connects come the next surrounding strand in the barrel v a lengthy right-handed loop that includes one of the helices, so that the ribbon N-to-C colour in the height view (A) proceeds in rainbow order roughly the barrel. The TIM barrel can likewise be believed of, then, as made up of 8 overlapping, right-handed β-α-β super-secondary structures, as shown in the side watch (B).