B. Alberts, A. Johnson, J. Lewis и др. - Molecular Biology of The Cell (6th edition) (1120996), страница 43
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The requirement that no twoatoms overlap plus other constraints limit the possible bond angles in a polypeptide chain (Figure 3–3), severely restricting the possible three-dimensionalMBoC6 m3.01/3.01arrangements (or conformations)of atoms. Nevertheless, a long flexible chainsuch as a protein can still fold in an enormous number of ways.The folding of a protein chain is also determined by many different sets ofweak noncovalent bonds that form between one part of the chain and another.These involve atoms in the polypeptide backbone, as well as atoms in the aminoacid side chains. There are three types of these weak bonds: hydrogen bonds, electrostatic attractions, and van der Waals attractions, as explained in Chapter 2 (seep. 44).
Individual noncovalent bonds are 30–300 times weaker than the typicalcovalent bonds that create biological molecules. But many weak bonds acting inparallel can hold two regions of a polypeptide chain tightly together. In this way,the combined strength of large numbers of such noncovalent bonds determinesthe stability of each folded shape (Figure 3–4).AMINO ACIDAspartic acidGlutamic acidArginineLysineHistidineAsparagineGlutamineSerineThreonineTyrosineAspGluArgLysHisAsnGlnSerThrTyrSIDE CHAINDERKHNQSTYAMINO ACIDnegativenegativepositivepositivepositiveuncharged polaruncharged polaruncharged polaruncharged polaruncharged polarAlanineGlycineValineLeucineIsoleucineProlinePhenylalanineMethionineTryptophanCysteinePOLAR AMINO ACIDSAlaGlyValLeuIleProPheMetTrpCysSIDE CHAINAGVLIPFMWCnonpolarnonpolarnonpolarnonpolarnonpolarnonpolarnonpolarnonpolarnonpolarnonpolarNONPOLAR AMINO ACIDSFigure 3–2 The 20 amino acids commonly found in proteins.
Each amino acid has a three-letter and a oneletter abbreviation. There are equal numbers of polar and nonpolar side chains; however, some side chains listedhere as polar are large enough to have some nonpolar properties (for example, Tyr, Thr, Arg, Lys). For atomicstructures, see Panel 3–1 (pp.
112–113).MBoC6 m3.02/3.02THE SHAPE AND STRUCTURE OF PROTEINS(A)111(B)amino acidH+180OR2HCCαNCαNR1HphiHpsiHCCαOR3psi 0peptide bondsFigure 3–3 Steric limitations on the bond angles in a polypeptidechain. (A) Each amino acid contributes three bonds (red) to the backboneof the chain. The peptide bond is planar (gray shading) and does not permitrotation. By contrast, rotation can occur about the Cα–C bond, whoseangle of rotation is called psi (ψ), and about the N–Cα bond, whose angle ofrotation is called phi (ϕ). By convention, an R group is often used to denotean amino acid side chain (purple circles).
(B) The conformation of the mainchain atoms in a protein is determined by one pair of ϕ and ψ angles for eachamino acid; because of steric collisions between atoms within each aminoacid, most of the possible pairs of ϕ and ψ angles do not occur. In this socalled Ramachandran plot, each dot represents an observed pair of angles ina protein. The three differently shaded clusters of dots reflect three different“secondary structures” repeatedly found in proteins, as will be described inthe text. (B, from J. Richardson, Adv. Prot. Chem. 34:174–175, 1981.© Academic Press.)–180–1800phi+180alpha helix(right-handed)beta sheetleft-handedhelixMBoC6 m3.03b/3.m3.03/3.03A fourth weak force—a hydrophobic clustering force—also hasMBoC6a centralrolein determining the shape of a protein.
As described in Chapter 2, hydrophobicmolecules, including the nonpolar side chains of particular amino acids, tend tobe forced together in an aqueous environment in order to minimize their disruptive effect on the hydrogen-bonded network of water molecules (see Panel 2–2,pp. 92–93). Therefore, an important factor governing the folding of any protein isglutamic acidNHHOCCelectrostaticattractionsCH2+RCH2COOHHHN+Chydrogen bondsOCCH2CH2van der Waals attractionsCH2COHlysineHNH CCH3 CH3CvalineCH3 CH3HCHNNHCROOC HHNCH3CNCHCHOC N CHHOHOHCRCH2CCHvalinealanineFigure 3–4 Three types of noncovalent bonds help proteins fold. Although a single one of these bonds is quite weak, manyof them act together to create a strong bonding arrangement, as in the example shown. As in the previous figure, R is used as ageneral designation for an amino acid side chain.PANEL 3–1: The 20 Amino Acids Found in Proteins112THE AMINO ACIDOPTICAL ISOMERSThe α-carbon atom is asymmetric, whichallows for two mirror images (or stereo-)isomers, L and D.The general formula of an amino acid isα-carbon atomHaminogroup H2NCcarboxylRHHCOOH groupCOO–NH3+side-chain groupLR is commonly one of 20 different side chains.At pH 7 both the amino and carboxyl groupsare ionized.H+H3N C COORCOO–NH3+CαCαRRDProteins consist exclusively of L-amino acids.PEPTIDE BONDSPeptide bond: The four atoms in each gray box form a rigidplanar unit.
There is no rotation around the C–N bond.Amino acids are commonly joined together by an amide linkage,called a peptide bond.HHNHCROCNOHHH2ORHCOHCNOHHHOCCHRRNCHHOCOHSHProteins are long polymersof amino acids linked bypeptide bonds, and theyare always written with theN-terminus toward the left.The sequence of this tripeptideis histidine-cysteine-valine.amino- orN-terminus+H N3HOCCCH2The common amino acidsare grouped according towhether their side chainsareacidicbasicuncharged polarnonpolarThese 20 amino acidsare given both three-letterand one-letter abbreviations.Thus: alanine = Ala = ANCCHHNCOHHNcarboxyl- orC-terminusCOO–CHCH3CCHHCFAMILIES OFAMINO ACIDSCH2NH+CH3These two single bonds allow rotation, so that long chains ofamino acids are very flexible.BASIC SIDE CHAINSlysineargininehistidine(Lys, or K)(Arg, or R)(His, or H)HONCCHCH2HONCCHCH2CH2CH2CH2+NH3HONCCHCH2CCH2This group isvery basicbecause itspositive chargeis stabilized byresonance.CH2HCNHC+H2NHNNH2CHNH+These nitrogens have arelatively weak affinity for anH+ and are only partly positiveat neutral pH.113ACIDIC SIDE CHAINSNONPOLAR SIDE CHAINSalaninevaline(Val, or V)aspartic acidglutamic acid(Ala, or A)(Asp, or D)(Glu, or E)HOCNHHOHONCCCCCHCH3NHCH2ONCCHCHCH3CH2CH3CH2CO–OHleucineCO–O(Leu, or L)HONCCHCH2CH3ONCCHCHCH2CH3CHUNCHARGED POLAR SIDE CHAINSHCH3CH3asparagineglutamineprolinephenylalanine(Asn, or N)(Gln, or Q)(Pro, or P)(Phe, or F)HONCCHCH2HONCCHCH2NH2OCCCH2CH2CH2CONHHONCCHCH2CH2(actually animino acid)CONH2Although the amide N is not charged atneutral pH, it is polar.methioninetryptophan(Met, or M)(Trp, or W)HONCCHCH2HONCCHCH2CH2Sserinethreoninetyrosine(Ser, or S)(Thr, or T)(Tyr, or Y)HNCHCH2OCOHHNCHCHOCCH3HNCHCH2OHOHThe –OH group is polar.OCCH3NHglycinecysteine(Gly, or G)(Cys, or C)HONCCHHHONCCHCH2SHDisulfide bonds can form between two cysteine side chainsin proteins.SCH2CH2 S114Chapter 3: Proteinsunfolded polypeptidenonpolarside chainspolarsidechainspolar side chain on theoutside of the moleculecan form hydrogenbonds to waterpolypeptidebackbonehydrophobic core regioncontains nonpolarside chainsfolded conformation in aqueous environmentthe distribution of its polar and nonpolar amino acids.
The nonpolar (hydrophobic) side chains in a protein—belonging to such amino acids as phenylalanine,leucine, valine, and tryptophan—tendMBoC6 m3.05/3.05to cluster in the interior of the molecule(just as hydrophobic oil droplets coalesce in water to form one large droplet). Thisenables them to avoid contact with the water that surrounds them inside a cell.In contrast, polar groups—such as those belonging to arginine, glutamine, andhistidine—tend to arrange themselves near the outside of the molecule, wherethey can form hydrogen bonds with water and with other polar molecules (Figure3–5). Polar amino acids buried within the protein are usually hydrogen-bonded toother polar amino acids or to the polypeptide backbone.Proteins Fold into a Conformation of Lowest EnergyAs a result of all of these interactions, most proteins have a particular three-dimensional structure, which is determined by the order of the amino acids in itschain.
The final folded structure, or conformation, of any polypeptide chain isgenerally the one that minimizes its free energy. Biologists have studied protein folding in a test tube using highly purified proteins. Treatment with certainsolvents, which disrupt the noncovalent interactions holding the folded chaintogether, unfolds, or denatures, a protein. This treatment converts the protein intoa flexible polypeptide chain that has lost its natural shape.
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