2 Структура и функция белка (1160071), страница 18
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TheRamachandran plot in Figure 7-5 shows the conformations permittedfor most amino acid residues.(d)rotate. Other single bonds in the backbone mayalso be rotationally hindered, depending on the sizeand charge of the R groups, (d) By convention, 4>and ip are both defined as 0° when the two peptidebonds flanking an a carbon are in the same plane.In a protein, this conformation is prohibited bysteric overlap between a carbonyl oxygen and ana-amino hydrogen atom.165+ 180120600-60 p-120-180-1800+ 180<b (degrees)Figure 7-5 A Ramachandran plot. The theoretically allowed conformations of peptides are shown,defined by the values of $ and ip.
The shaded areasreflect conformations that can be take up by allamino acids (dark shading) or all except valine andisoleucine (medium shading); the lightest shadingreflects conformations that are somewhat unstablebut are found in some protein structures.Part II Structure and Catalysis166The a Helix Is a Common Protein Secondary StructurePauling and Corey were aware of the importance of hydrogen bonds inorienting polar chemical groups such as the —C=O and —N—Hgroups of the peptide bond. They also had the experimental results ofWilliam Astbury, who in the 1930s had conducted pioneering x-raystudies of proteins.
Astbury demonstrated that the protein that makesup hair and wool (the fibrous protein a-keratin) has a regular structurethat repeats every 0.54 nm. With this information and their data onthe peptide bond, and with the help of precisely constructed models,Pauling and Corey set out to determine the likely conformations ofprotein molecules.The simplest arrangement the polypeptide chain could assumewith its rigid peptide bonds (but with the other single bonds free torotate) is a helical structure, which Pauling and Corey called the ahelix (Fig.
7-6). In this structure the polypeptide backbone is tightlywound around the long axis of the molecule, and the R groups of theamino acid residues protrude outward from the helical backbone. Therepeating unit is a single turn of the helix, which extends about0.56 nm along the long axis, corresponding closely to the periodicityCarbono HydrogenQ OxygenQ Nitrogen(a)(b)Figure 7-6 Four models of the a helix, showingdifferent aspects of its structure, (a) Formation ofa right-handed a helix. The planes of the rigid peptide bonds are parallel to the long axis of the helix.(b) Ball-and-stick model of a right-handed a helix,showing the intrachain hydrogen bonds.
The repeatunit is a single turn of the helix, 3.6 residues.(c) The a helix as viewed from one end, lookingdown the longitudinal axis. Note the positions ofthe R groups, represented by red spheres, (d) Aspace-filling model of the a helix.(c)(d)Chapter 7 The Three-Dimensional Structure of ProteinsBOX 7-1Knowing the Right Hand from the LeftThere is a simple method for determining thehandedness of a helical structure, whether righthanded or left-handed. Make fists of your twohands with thumbs outstretched and pointingaway from you.
Looking at your right hand, thinkof a helix spiraling away in the direction indicatedby your right thumb, and the spiral occurring inthe direction in which the other four fingers arecurled as shown (clockwise). The resulting helix isright-handed. Repeating the process with your lefthand will produce an image of a left-handed helix,which rotates in the counterclockwise direction asit spirals away from you.Astbury observed on x-ray analysis of hair keratin. The amino acidresidues in an a helix have conformations with if/ = -45° to -50° and(/> = -60°, and each helical turn includes 3.6 amino acids. The twistingof the helix has a right-handed sense (Box 7-1) in the most commonform of the a helix, although a very few left-handed variants have beenobserved.The a helix is one of two prominent types of secondary structure inproteins.
It is the predominant structure in a-keratins. In globularproteins, about one-fourth of all amino acid residues are found in ahelices, the fraction varying greatly from one protein to the next.Why does such a helix form more readily than many other possibleconformations? The answer is, in part, that it makes optimal use ofinternal hydrogen bonds. The structure is stabilized by a hydrogenbond between the hydrogen atom attached to the electronegative nitrogen atom of each peptide linkage and the electronegative carbonyl oxygen atom of the fourth amino acid on the amino-terminal side of it inthe helix (Fig.
7-6b). Every peptide bond of the chain participates insuch hydrogen bonding. Each successive coil of the a helix is held to theadjacent coils by several hydrogen bonds, which in summation give theentire structure considerable stability.Further model-building experiments have shown that an a helixcan form with either L- or D-amino acids. However, all residues must beof one stereoisomeric series; a D-amino acid will disrupt a regularstructure consisting of L-amino acids, and vice versa.
Naturally occurring L-amino acids can form either right- or left-handed helices, but,with rare exceptions, only right-handed helices are found in proteins.167Part II Structure and Catalysis168Amino Acid Sequence Affects a Helix StabilityFigure 7—7 Interactions between R groups ofamino acids three residues apart in an a helix. Anionic interaction between Asp100 and Arg103 in ana-helical region of the protein troponin C is shownin this space-filling model. The polypeptide backbone (carbons, a-amino nitrogens, and a-carbonyloxygens) is shown in white for a helix segmentabout 12 amino acids long.
The ronly side chainsshown are the interacting Asp and Arg residues,with the aspartate in red and the arginine in blue.The side chain interaction illustrated occurs withinthe white connecting helix in Fig. 7-3.+4<rf+Not all polypeptides can form a stable a helix. Additional interactionsoccur between amino acid side chains that can stabilize or destabilizethis structure. For example, if a polypeptide chain has many Glu residues in a long block, this segment of the chain will not form an a helixat pH 7.0. The negatively charged carboxyl groups of adjacent Glu residues repel each other so strongly that they overcome the stabilizinginfluence of hydrogen bonds on the a helix.
For the same reason, ifthere are many adjacent Lys and/or Arg residues, with positivelycharged R groups at pH 7.0, they will also repel each other and preventformation of the a helix. The bulk and shape of certain R groups canalso destabilize the a helix or prevent its formation. For example, Asn,Ser, Thr, and Leu residues tend to prevent formation of the a helix ifthey occur close together in the chain.The twist of an a helix ensures that critical interactions occur between an amino acid side chain and the side chain three (and sometimes four) residues away on either side of it (Fig. 7-7). Positivelycharged amino acids are often found three residues away from negatively charged amino acids, permitting the formation of an ionic interaction. Two aromatic amino acids are often similarly spaced, resultingin a hydrophobic interaction.A minor constraint on the formation of the a helix is the presenceof Pro residues.
In proline the nitrogen atom is part of a rigid ring (Fig.5-6), and rotation about the N—Ca bond is not possible. In addition,the nitrogen atom of a Pro residue in peptide linkage has no substituent hydrogen-to-hydrogen bond with other residues. For these reasons,proline is only rarely found within an a helix.A final factor affecting the stability of an a helix is the identity ofthe amino acids located near the ends of the a-helical segment of apolypeptide.
A small electric dipole exists in each peptide bond (seeFig. 7-4). These dipoles add across the hydrogen bonds in the helix sothat the net dipole increases as helix length increases (Fig. 7-8). Thefour amino acids at either end of the helix do not participate fully in thehelix hydrogen bonds. The partial positive and negative charges of thehelix dipole actually reside on the peptide amino and carbonyl groupsnear the amino-terminal and carboxyl-terminal ends of the helix, respectively. For this reason, negatively charged amino acids are oftenfound near the amino terminus of the helical segment, where theyhave a stabilizing interaction with the positive charge of the helix dipole; a positively charged amino acid at the amino-terminal end isdestabilizing.
The opposite is true at the carboxyl-terminal end of thehelical segment.Figtire 7—8 The electric dipole of a peptide bond(Fig. 7—4a) is transmitted along an a-helical segment through the intrachain hydrogen bonds, resulting in an overall helix dipole. In this illustration, the amino and carbonyl constituents of eachpeptide bond are indicated by + and - symbols,respectively. Unbonded amino and carbonyl constituents in the peptide bonds near either end of thea-helical region are shown in red.Chapter 7 The Three-Dimensional Structure of Proteins169Thus there are five different kinds of constraints that affect thestability of an a helix: (1) the electrostatic repulsion (or attraction)between amino acid residues with charged R groups, (2) the bulkinessof adjacent R groups, (3) the interactions between amino acid sidechains spaced three (or four) residues apart, (4) the occurrence of Proresidues, and (5) the interaction between amino acids at the ends of thehelix and the electric dipole inherent to this structure.The P Conformation OrganizesPolypeptide Chains into SheetsPauling and Corey predicted a second type of repetitive structure, theP conformation.
This is the more extended conformation of the polypeptide chains, as seen in the silk protein fibroin (a member of a classof fibrous proteins called /3-keratins), and its structure has been confirmed by x-ray analysis. In the /3 conformation, which like the a helixis common in proteins, the backbone of the polypeptide chain is extended into a zigzag rather than helical structure (Fig. 7-9).
In fibrointhe zigzag polypeptide chains are arranged side by side to form a structure resembling a series of pleats; such a structure is called a (3 pleatedsheet. In the (3 conformation the hydrogen bonds can be either intrachain, or interchain between the peptide linkages of adjacent polypeptide chains. All the peptide linkages of /3-keratin participate in interchain hydrogen bonding. The R groups of adjacent amino acidsprotrude in opposite directions from the zigzag structure, creating analternating pattern as seen in the side view (Fig. 7-9c).Figure 7-9 The /3 conformation of polypeptidechains.
Views show the R groups extending outfrom the /3 pleated sheet and emphasize the pleatedsheet described by the planes of the peptide bonds.Hydrogen-bond cross-links between adjacent chainsare also shown, (a) Antiparallel fi sheets, in whichthe amino-terminal to carboxyl-terminal orientationof adjacent chains (arrows) is inverse, (b) ParallelP sheets, (c) Silk fibers are made up of the proteinfibroin. Its structure consists of layers of antiparallel /3 sheets rich in Ala (purple) and Gly (yellow)residues. The small side chains interdigitate andallow close packing of each layered sheet, as shownin this side view.0.35 nm T^v0.57 nmAlanine side chainGlycine side chain(c)Antiparallel(a)170Part II Structure and CatalysisThe adjacent polypeptide chains in a /3 pleated sheet can be eitherparallel (having the same amino-to-carboxyl polypeptide orientation) or antiparallel (having the opposite amino-to-carboxyl orientation).
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