Principles and Patterns of Protein Conformation

  • Jane S. Richardson
  • David C. Richardson

Abstract

The raw materials of protein structure are the detailed geometry and chemistry of the polypeptide and side chains plus the solvent environment. The end result is a complex tapestry of details organized into a biologically meaningful whole: a variation on one of a few harmonious themes of three-dimensional structure. For the purposes of prediction we are not concerned primarily with either of the endpoints of this process but with the logical connection between the two. Therefore, we summarize what is known of that logical connection into a set of guiding principles: hydrophobicity, hydrogen bonding, handedness, history, and the tension between hierarchy and interrelatedness. In addition, we consider particularly relevant features of the starting and ending states. However, one should bear in mind, as cartooned in Fig. 1, that our abilities to follow the protein through this remarkable transition are still rather limited in both the experimental and the theoritical realms.

Keywords

Entropy Cysteine Serine Polypeptide Arginine 

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References

  1. Abdel-Meguid, S., Shieh, H.-S., Smith, W., Dayringer, H., Violand, B., and Bentle, L., 1987, Three-dimensional structure of a genetically engineered variant of porcine growth hormone, Proc. Natl. Acad. Sci. U.S.A. 84:6434–6437.PubMedGoogle Scholar
  2. Alber, T., Banner, D., Bloomer, A., Petsko, G., Phillips, D., Rivers, P., and Wilson, I., 1981, On the three-dimensional structure and catalytic mechanism of triose phosphate isomerase, Phil. Trans. R. Soc. Lond. [Biol.] 293:159–171.Google Scholar
  3. Anderson, A., and Hermans, J., 1988, Microfolding: Conformational probability map for the alanine dipeptide in water from molecular dynamics simulations, Proteins 3:262–265.PubMedGoogle Scholar
  4. Anderson, C., Stenkamp, R., McDonald, R., and Steitz, T., 1978, A refined model of the sugar binding site of yeast hexokinase B, J. Mol. Biol. 123:207–210.PubMedGoogle Scholar
  5. Argos, P., and Palau, J., 1982, Amino acid distribution in protein secondary structures, Int. J. Peptide Protein Res. 19:380–393.Google Scholar
  6. Argos, P., Rossman, M., and Johnson, J., 1977, A four-helical super-secondary structure, Biochem. Biophy. Res. Commun. 75:83–86.Google Scholar
  7. Baker, E., and Hubbard, R., 1984, Hydrogen bonding in globular proteins, Prog. Biophys. Mol. Biol. 44:97–179.PubMedGoogle Scholar
  8. Banner, D., Kokkinidis, M., and Tsemoglou, D., 1987, The structure of the ColE1 ROP protein at 1.7Å resolution, J. Mol. Biol. 196:657–675.PubMedGoogle Scholar
  9. Bernstein, F., Koetzle, T., Williams, G., Meyer, E., Jr., Brice, M., Rodgers, J., Kennard, O., Shimanouchi, T., and Tasumi, M., 1977, The Protein Data Bank: A computer-based archival file for macromolecular structures, J. Mol. Biol. 112:535–542.PubMedGoogle Scholar
  10. Blanc, J., and Kaiser, E., 1984, Biological and physical properties of a ß-endorphin analog containing only Ũ-amino acids in the amphiphilic helical segment 13–31, J. Biol. Chem. 259:9549–9556.PubMedGoogle Scholar
  11. Blundell, T., Lindley, P., Miller, L., Moss, D., Slingsby, C., Tickle, I., Turnell, B., and Wistow, G., 1981, The molecular structure and stability of the eye lens: X-ray analysis of gamma-crystallin II, Nature 289: 771–777.PubMedGoogle Scholar
  12. Blundell, T., Singh, J., Thornton, J., Burley, S., and Petsko, G., 1986, Aromatic interactions, Science 234: 1005.Google Scholar
  13. Blundell, T., Sibanda, B., Sternberg, M., and Thornton, J., 1987, Knowledge-based prediction of protein structures and the design of novel molecules, Nature 326:347–352.PubMedGoogle Scholar
  14. Brandts, J., Halvorson, H., and Brennan, M., 1975, Consideration of the possibility that the slow step in protein denaturation reactions is due to cis-trans isomerism of proline residues, Biochemistry 14:4953–4963.PubMedGoogle Scholar
  15. Braun, W., Wagner, G., Wörgötter, E., Vašák, M., Kägi, J., and Wüthrich, K., 1986, Polypeptide fold in the two metal clusters of metallothionein-2 by nuclear magnetic resonance in solution, J. Mol. Biol. 187:125–129.PubMedGoogle Scholar
  16. Bryan, P., Rollence, M., Pantoliano, M., Wood, J., Finzel, B., Gilliland, G., Howard, A., and Poulos, T., 1986, Proteases of enhanced stability: Characterization of a thermostable variant of subtilisin, Proteins 1: 326–334.PubMedGoogle Scholar
  17. Chothia, C., 1973, Conformation of twisted ß-pleated sheets in proteins, J. Mol. Biol. 75:295–302.PubMedGoogle Scholar
  18. Chothia, C., 1976, The nature of the accessible and buried surfaces in proteins, J. Mol. Biol. 105:1–14.PubMedGoogle Scholar
  19. Chothia, C., 1983, Coiling of ß-pleated sheets, J. Mol. Biol. 163:107–117.PubMedGoogle Scholar
  20. Chothia, C., and Janin, J., 1981, Relative orientation of close-packed ß-pleated sheets in proteins, Proc. Natl. Acad. Sci. U.S.A. 78:4146–4150.PubMedGoogle Scholar
  21. Chothia, C., Levitt, M., and Richardson, D., 1977, Structure of proteins: Packing of α-helices and pleated sheets, Proc. Natl. Acad. Sci. U.S.A. 74:4130–4134.PubMedGoogle Scholar
  22. Chou, P., and Fasman, G., 1977, ß-Turns in proteins, J. Mol. Biol. 115:135–175.PubMedGoogle Scholar
  23. Chou, K.-C., Némethy. G.. Pottle, M., and Scheraga. H.. 1989 J. Mol. Biol. 205:241–249.PubMedGoogle Scholar
  24. Cook, W., Einspahr, H., Trapane, T., Urry, D., and Bugg, C., 1980, The crystal structure and conformation of the cyclic trimer of a repeat pentapeptide of elastin: Cyclo L Val-L Pro-Gly-L Val-Gly, J. Am. Chem. Soc. 102:5502–5505.Google Scholar
  25. Creighton, T., 1977, Conformational restrictions on the pathway of folding and unfolding of the pancreatic trypsin inhibitor, J. Mol. Biol. 113:275–293.PubMedGoogle Scholar
  26. DeGrado, W., Musso, G., Lieber, M., Kaiser, E., and Kezdy, F., 1982, Kinetics and mechanism of hemolysis induced by melittin and by a synthetic melittin analogue, Biophys. J. 37:329–338.PubMedGoogle Scholar
  27. Deisenhofer, J., Jones, T., Huber, R., Sjodahl, J., and Sjoquist, J., 1978, Crystallization, crystal structure analysis and atomic model of the complex formed by a human Fc fragment and fragment B of protein A from Staphylococcus aureus, Hoppe Zeylers Z. Physiol. Chem. 359:975–985.Google Scholar
  28. Deisenhofer, J., Epp, O., Miki, K., Huber, R., and Michel, H., 1985, Structure of the protein subunits in the photosynthetic reaction center of Rhodopseudornonas viridis at 3Å resolution, Nature 318:618–624.Google Scholar
  29. Edwards, M., Sternberg, M., and Thornton, J., 1987, Structural and sequence patterns in the loops of ßαß units, Protein Eng. 1:173–181.PubMedGoogle Scholar
  30. Efimov, A., 1982, Role of constrictions in formation of protein structures containing four helical regions, Mol. Biol. (Mosk.) 16:271–281.Google Scholar
  31. Eisenberg, D., Weiss, R., and Terwilliger, T., 1982, The helical hydrophobic moment: A measure of the amphiphilicity of a helix, Nature 299:371–374.PubMedGoogle Scholar
  32. Engelman, D., Henderson, R., McLachlan, A., and Wallace, B., 1980, Path of the polypeptide in bacteriorhodopsin, Proc. Natl. Acad. Sci. U.S.A. 77:2023–2027.PubMedGoogle Scholar
  33. Epstein, C., Goldberger, R., and Anfinsen, C., 1963, The genetic control of tertiary protein structure: Studies with model systems, Cold Spring Harbor Symp. Quant. Biol. 28:439–449.Google Scholar
  34. Ghosh, S., Bock, S., Rokita, S., and Kaiser, E., 1986, Modification of the active site of alkaline phosphatase by site-directed mutagenesis, Science 231:145–148.PubMedGoogle Scholar
  35. Grathwohl, C., and Wüthrich, K., 1974, Carbon-13 NMR of the protected tetrapeptides TFA-Gly-GlY-L-X-L-Ala-OCH3, where X stands for the 20 common amino acids, J. Magnet. Res. 13:217–225.Google Scholar
  36. Hecht, M., Sturtevant, J., and Sauer, R., 1986, Stabilization of lambda repressor against thermal denaturation by site-directed Gly → Ala changes in α-helix 3, Proteins 1:43–46.PubMedGoogle Scholar
  37. Hol, W., van Duijnen, P., and Berendsen, H., 1978, The α-helix dipole and the properties of proteins, Nature 273:443–446.PubMedGoogle Scholar
  38. Honig, B., Hubbell, W., and Flewelling, R., 1986, Electrostatic interactions in membranes and proteins, Annu. Rev. Biophys. Bioeng. 15:163–193.Google Scholar
  39. IUPAC-IUB Commission on Biochemical Nomenclature, 1970, Abbreviations and symbols for the description of the conformation of polypeptide chains, J. Biol. Chem. 245:6489–6497.Google Scholar
  40. James, M., and Sielecki, A., 1983, Structure and refinement of penicillopepsin at 1.8Å resolution, J. Mol. Biol. 163:299–361.PubMedGoogle Scholar
  41. Janin, J., 1979, Surface and inside volumes in globular proteins, Nature 277:491–492.PubMedGoogle Scholar
  42. Janin, J., and Wodak, S., 1978, Conformation of amino acid side-chains in proteins, J. Mol. Biol. 125:357–386.PubMedGoogle Scholar
  43. Kabsch, W., and Sander, C., 1983, Dictionary of protein secondary structure: Pattern recognition of hydrogen-bonded and geometrical features, Biopolymers 22:2577–2637.PubMedGoogle Scholar
  44. Karle, I., Kishore, R., Raghothama, S., and Balaram, P., 1988, Cyclic cystine peptides: Antiparallel ß-sheet conformation for the 20-membered ring in BOC-Cys-Val-Aib-Ala-Leu-Cys-NHMe, J. Am. Chem. Soc. 110:1958–1963.Google Scholar
  45. Kauzmann, W., 1959, Some factors in the interpretation of protein denaturation, Adv. Protein Chem. 14:1–63.PubMedGoogle Scholar
  46. Kendrew, J., Watson, H., Stranberg, B., and Dickerson, R., 1961, The amino-acid sequence of sperm whale myoglobin: A partial determination by x-ray methods, and its correlation with chemical data, Nature 190: 666–670.PubMedGoogle Scholar
  47. Kline, A., Braun, W., and Wüthrich, K., 1986, Studies by 1H nuclear magnetic resonance and distance geometry of the solution conformation of the α-amylase inhibitor Tendamistat, J. Mol. Biol. 189: 377–382.PubMedGoogle Scholar
  48. Kretsinger, R., and Nockolds, C., 1973, Carp muscle calcium-binding protein, J. Biol. Chem. 248:3313–3326.PubMedGoogle Scholar
  49. Kyte, J., and Doolittle, R., 1982, A simple method for displaying the hydropathic character of a protein, J. Mol. Biol. 157: 105–132.PubMedGoogle Scholar
  50. Lesk, A., and Chothia, C., 1980, How different amino acids determine similar protein structures: The structure and evolutionary dynamics of the globins, J. Mol. Biol. 136:225–270.PubMedGoogle Scholar
  51. Lesk, A., and Chothia, C., 1984, Mechanisms of domain closure in proteins, J. Mol. Biol. 174:175–191.PubMedGoogle Scholar
  52. Leszczynski, J., and Rose, G., 1986, Loops in globular proteins: A novel category of secondary structure, Science 234:849–855.PubMedGoogle Scholar
  53. Levitt, M., and Greer, J., 1977, Automatic identification of secondary structure in globular proteins, J. Mol. Biol. 114:181–239.PubMedGoogle Scholar
  54. Lewis, P., Momany, F., and Scheraga, H., 1973, Chain reversals in proteins, Biochim. Biophys. Acta 303:211–229.PubMedGoogle Scholar
  55. Lifson, S., and Sander, C., 1979, Antiparallel and parallel ß-strands differ in amino acid residue preferences, Nature 282: 109–111.PubMedGoogle Scholar
  56. Lifson, S., and Sander, C., 1980, Specific recognition in the tertiary structure of ß-sheets of proteins, J. Mol. Biol. 139:627–639.PubMedGoogle Scholar
  57. Low, B., Preston, H., Sato, A., Rosen, L., Searl, J., Rudko, A., and Richardson, J., 1976, Three dimensional structure of erabutoxin b neurotoxic protein: Inhibitor of acetylcholine receptor, Proc. Natl. Acad. Sci. U.S.A. 73:2991–2994.PubMedGoogle Scholar
  58. Matthews, B., Nicholson, H., and Becktel, W., 1987, Enhanced protein thermostability from site-directed mutations that decrease the entropy of unfolding, Proc. Natl. Acad. Sci. U.S.A. 84:6663–6667.PubMedGoogle Scholar
  59. McPhalen, C., 1986, X-ray Crystallographic Studies on Subtilisins and Their Protein Inhibitors, Ph. D. thesis, University of Alberta, Edmonton.Google Scholar
  60. McPhalen, C., Schnebli, H., and James, M., 1985, Crystal and molecular structure of the inhibitor eglin from leeches in complex with subtilisin Carlsberg, FEBS Lett. 188:55–58.PubMedGoogle Scholar
  61. Momany, F., McGuire, R., Burgess, A., and Scheraga, H., 1975, Energy parameters in polypeptides. VII. Geometric parameters, partial atomic charges, nonbonded interactions, and intrinsic torsional potentials for the naturally occurring amino acids, J. Phys. Chem. 79:2361–2380.Google Scholar
  62. Nakashima, H., Nishikawa, K., and Ooi, T., 1986, The folding type of a protein is relevant to the amino acid composition, J. Biochem. (Tokyo) 99:153–162.Google Scholar
  63. Newcomer, M., Jones, T., Åqvist, J., Sundelin, J., Eriksson, U., Rask, L., and Peterson, P., 1984, The three-dimensional structure of retinol-binding protein, EMBO J. 3:1451–1454.PubMedGoogle Scholar
  64. Pabo, C., Sauer, R., Sturtevant, J., and Ptashne, M., 1979, The lambda repressor contains two domains, Proc. Natl. Acad. Sci. U.S.A. 76:1608–1612.PubMedGoogle Scholar
  65. Pflugrath, J., and Quiocho, F., 1985, Sulphate sequestered in the sulphate-binding protein of Salmonella typhimurium is bound solely by hydrogen bonds, Nature 314:257–260.PubMedGoogle Scholar
  66. Ptitsyn, O., 1969, Statistical analysis of the distribution of amino acid residues among helical and non-helical regions in globular proteins, J. Mol. Biol. 42:501–510.PubMedGoogle Scholar
  67. Ptitsyn, O., and Finkelstein, A., 1980, Self-organization of proteins and the problem of their three-dimensional structure prediction, in: Protein Folding (R. Jaenicke, ed.), Elsevier, Amsterdam, pp. 101–115.Google Scholar
  68. Rao, S., and Rossmann, M., 1973, Comparison of super-secondary structures in proteins, J. Mol. Biol. 76:241–256.PubMedGoogle Scholar
  69. Rees, D., Lewis, M., and Lipscomb, W., 1983, Refined crystal structure of carboxypeptidase A at 1.54Å resolution, J. Mol. Biol. 168:367–387.PubMedGoogle Scholar
  70. Rice, D., Ford, G., White, J., Smith, J., and Harrison, P., 1983, The spatial structure of horse spleen apoferritin, Adv. Inorg. Biochem. 5:39–50.Google Scholar
  71. Rich, A., and Crick, F., 1961, The molecular structure of collagen, J. Mol. Biol. 3:483–506.PubMedGoogle Scholar
  72. Richardson, J., 1976, Handedness of crossover connections in ß sheets, Proc. Natl. Acad. Sci. 73:2619–2623.PubMedGoogle Scholar
  73. Richardson, J., 1977, ß-sheet topology and the relatedness of proteins, Nature 268:495–500.PubMedGoogle Scholar
  74. Richardson, J., 1981, The anatomy and taxonomy of protein structure, Adv. Protein Chem. 34:167–339.PubMedGoogle Scholar
  75. Richardson, J., 1985, Schematic drawings of protein structures, in: Methods in Enzymology, Vol. 115B, Chapter 24 (H. Wyckoff, C. Hirs, and S. Timasheff, eds.), Academic Press, Orlando, pp. 359–380.Google Scholar
  76. Richardson, J., and Richardson, D., 1987, Some design principles: Betabellin, in: Protein Engineering, Chapter 12 (D. Oxender and C. Fox, eds.), Alan R. Liss, New York, pp. 149–163,340-341.Google Scholar
  77. Richardson, J., and Richardson, D., 1988a, Amino acid preferences for specific locations at the end of α-helices, Science 240:1648–1652.PubMedGoogle Scholar
  78. Richardson, J., and Richardson, D., 1988b, Helix lap-joints as ion-bonding sites, Proteins 4:229–239.PubMedGoogle Scholar
  79. Richmond, T., and Richards, F., 1978, Packing of α-helices: Geometrical constraints and contact areas, J. Mol. Biol. 119:537–555.PubMedGoogle Scholar
  80. Richardson, J., Getzoff, E., and Richardson, D., 1978, The α bulge: A common small unit of nonrepetitive protein structure, Proc. Natl. Acad. Sci. U.S.A. 75:2574–2578.PubMedGoogle Scholar
  81. Rose, G., 1978, Prediction of chain turns in globular proteins on a hydrophobic basis, Nature 272:586–590.PubMedGoogle Scholar
  82. Rose, G., 1979, Hierarchic organization of domains in globular proteins, J. Mol. Biol. 134:447–470.PubMedGoogle Scholar
  83. Rose, G., and Seltzer, J., 1977, A new algorithm for finding the peptide chain turns in a globular protein, J. Mol. Biol. 113:153–164.PubMedGoogle Scholar
  84. Rose, G., Geselowitz, A., Lesser, G., Lee, R., and Zehfus, M., 1985, Hydrophobicity of amino acid residues in globular proteins, Science 229:834–838.PubMedGoogle Scholar
  85. Salemme, F., 1983, Structural properties ofprotein ß-sheets, Prog. Biophys. Mol. Biol. 42:95–133.PubMedGoogle Scholar
  86. Salemme, F., and Weatherford, D., 1981, Conformational and geometrical properties of ß-sheets in proteins: II. Antiparallel and mixed ß-sheets, J. Mol. Biol. 146:119–141.PubMedGoogle Scholar
  87. Schellman, C., 1980, The αL conformation at the ends of helices, in: Protein Folding (R. Jaenicke, ed.), Elsevier, Amsterdam, pp. 53–61.Google Scholar
  88. Schiffer, M., and Edmundson, A., 1967, Use of helical wheels to represent the structure of proteins and to identify segments of helical potential, Biophys. J. 7:121–135.PubMedGoogle Scholar
  89. Sheridan, R., Lee, R., Peters, N., and Allen, L., 1979, Hydrogen-bond cooperativity in protein secondary structure, Biopolymers 18:2451–2458.Google Scholar
  90. Shoemaker, K., Kim, P., York, E., and Baldwin, R., 1987, Tests of the helix dipole model for stabilization of α-helices, Nature 326:563–567.PubMedGoogle Scholar
  91. Shortle, D., and Lin, B., 1985, Genetic analysis of staphylococcal nuclease: Identification of three intragenic “global” suppressors of nuclease-minus mutations, Genetics 110:539–555.PubMedGoogle Scholar
  92. Sibanda, B., and Thornton, J., 1985, ß-Hairpin families in globular proteins, Nature 316:170–174.PubMedGoogle Scholar
  93. Sprang, S., Standing, T., Fletterick, R., Stroud, R., Finer-Moore, J., Xuong, N.-H., Hamlin, R., Rutter, W., and Craik, C., 1987, Tbe three-dimensional structure of Asn102 mutant of trypsin: Role of Asp102 in serine protease catalysis, Science 237:905–909.PubMedGoogle Scholar
  94. Steitz, T., Ohlendorf, D., McKay, D., Anderson, W., and Matthews, B., 1982, Structural similarity in the DNA-binding domains of catabolite gene activator and cro repressor proteins, Proc. Natl. Acad. Sci. U.S.A. 79:3097–3100.PubMedGoogle Scholar
  95. Sternberg, M., and Thornton, J., 1977, On the conformation of proteins: Tbe handedness of the connection between parallel ß-strands, J. Mol. Biol. 110:269–283.PubMedGoogle Scholar
  96. Tainer, J., Getzoff, E., Beem, K., Richardson, J., and Richardson, D., 1982, Determination and analysis of the 2Å structure of copper, zinc superoxide dismutase, J. Mol. Biol. 160:181–217.PubMedGoogle Scholar
  97. Taylor, W., and Thornton, J., 1983, Prediction of super-secondary structure in proteins, Nature 301:540–542.PubMedGoogle Scholar
  98. Teeter, M. M., 1984, Water structure of a hydrophobic protein at atomic resolution: Pentagon rings of water molecules in crystals of crambin, Proc. Natl. Acad. Sci. U.S.A. 81:6014–6018.PubMedGoogle Scholar
  99. Venkatachalam, M., 1968, Stereochemical criteria for polypeptides and proteins: Conformation of a system of three linked peptide units, Biopolymers 6:1425–1436.PubMedGoogle Scholar
  100. Weber, P., and Salemme, F., 1980, Structural and functional diversity in 4-α-helical proteins, Nature 287:82–84.PubMedGoogle Scholar
  101. Wetlaufer, D. B., 1973, Nucleation, rapid folding, and globular intrachain regions in proteins, Proc. Natl. Acad. Sci. U.S.A. 70:697–701.PubMedGoogle Scholar
  102. Wilson, I., Haft, D., Getzoff, E., Tainer, J., Lerner, R., and Brenner, S., 1985, Identical short peptide sequences in unrelated proteins can have different conformations: A testing ground for theories of immune recognition, Proc. Natl. Acad. Sci. U.S.A. 82:5255–5259.PubMedGoogle Scholar
  103. Wolfenden, R., Andersson, L., Cullis, P., and Southgate, C., 1981, Affinities of amino acid side chains for solvent water, Biochemistry 20:849–855.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • Jane S. Richardson
    • 1
  • David C. Richardson
    • 1
  1. 1.Department of BiochemistryDuke UniversityDurhamUSA

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