Harpers

PROTEINS: HIGHER ORDERS OF STRUCTURE / 31THE FOUR ORDERS OFPROTEIN STRUCTUREThe modular nature of protein synthesis and foldingare embodied in the concept of orders of protein structure:primary structure, the sequence of the aminoacids in a polypeptide chain; secondary structure, thefolding of short (3- to 30-residue), contiguous segmentsof polypeptide into geometrically ordered units; tertiarystructure, the three-dimensional assembly of secondarystructural units to form larger functional unitssuch as the mature polypeptide and its component domains;and quaternary structure, the number andtypes of polypeptide units of oligomeric proteins andtheir spatial arrangement.SECONDARY STRUCTUREPeptide Bonds Restrict PossibleSecondary ConformationsFree rotation is possible about only two of the three covalentbonds of the polypeptide backbone: the α-carbon(Cα) to the carbonyl carbon (Co) bond and theCα to nitrogen bond (Figure 3–4). The partial doublebondcharacter of the peptide bond that links Co to theα-nitrogen requires that the carbonyl carbon, carbonyloxygen, and α-nitrogen remain coplanar, thus preventingrotation. The angle about the Cα⎯N bond istermed the phi (Φ) angle, and that about the Co⎯Cαbond the psi (Ψ) angle. For amino acids other thanglycine, most combinations of phi and psi angles aredisallowed because of steric hindrance (Figure 5–1).The conformations of proline are even more restricteddue to the absence of free rotation of the N⎯Cα bond.Regions of ordered secondary structure arise when aseries of aminoacyl residues adopt similar phi and psiangles. Extended segments of polypeptide (eg, loops)can possess a variety of such angles. The angles that definethe two most common types of secondary structure,the helix and the sheet, fall within the lowerand upper left-hand quadrants of a Ramachandranplot, respectively (Figure 5–1).The Alpha HelixThe polypeptide backbone of an α helix is twisted byan equal amount about each α-carbon with a phi angleof approximately −57 degrees and a psi angle of approximately−47 degrees. A complete turn of the helix containsan average of 3.6 aminoacyl residues, and the distanceit rises per turn (its pitch) is 0.54 nm (Figure5–2). The R groups of each aminoacyl residue in an αhelix face outward (Figure 5–3). Proteins contain onlyL-amino acids, for which a right-handed α helix is byfar the more stable, and only right-handed α helicesψ900– 90– 90 090φFigure 5–1. Ramachandran plot of the main chainphi (Φ) and psi (Ψ) angles for approximately 1000nonglycine residues in eight proteins whose structureswere solved at high resolution. The dots represent allowablecombinations and the spaces prohibited combinationsof phi and psi angles. (Reproduced, with permission,from Richardson JS: The anatomy and taxonomyof protein structures. Adv Protein Chem 1981;34:167.)occur in nature. Schematic diagrams of proteins representα helices as cylinders.The stability of an α helix arises primarily from hydrogenbonds formed between the oxygen of the peptidebond carbonyl and the hydrogen atom of the peptidebond nitrogen of the fourth residue down thepolypeptide chain (Figure 5–4). The ability to form themaximum number of hydrogen bonds, supplementedby van der Waals interactions in the core of this tightlypacked structure, provides the thermodynamic drivingforce for the formation of an α helix. Since the peptidebond nitrogen of proline lacks a hydrogen atom to contributeto a hydrogen bond, proline can only be stablyaccommodated within the first turn of an α helix.When present elsewhere, proline disrupts the conformationof the helix, producing a bend. Because of itssmall size, glycine also often induces bends in α helices.Many α helices have predominantly hydrophobic Rgroups on one side of the axis of the helix and predominantlyhydrophilic ones on the other. These amphipathichelices are well adapted to the formation of interfacesbetween polar and nonpolar regions such as thehydrophobic interior of a protein and its aqueous envi-