Skip to main content
PMC home page
Protein Science : A Publication of the Protein Society logoLink to Protein Science : A Publication of the Protein Society
. 1994 Dec;3(12):2395–2410. doi: 10.1002/pro.5560031223

Conservation of polyproline II helices in homologous proteins: implications for structure prediction by model building.

A A Adzhubei 1, M J Sternberg 1
PMCID: PMC2142760  PMID: 7756993

Abstract

Left-handed polyproline II (PPII) helices commonly occur in globular proteins in segments of 4-8 residues. This paper analyzes the structural conservation of PPII-helices in 3 protein families: serine proteinases, aspartic proteinases, and immunoglobulin constant domains. Calculations of the number of conserved segments based on structural alignment of homologous molecules yielded similar results for the PPII-helices, the alpha-helices, and the beta-strands. The PPII-helices are consistently conserved at the level of 100-80% in the proteins with sequence identity above 20% and RMS deviation of structure alignments below 3.0 A. The most structurally important PPII segments are conserved below this level of sequence identity. These results suggest that the PPII-helices, in addition to the other 2 secondary structure classes, should be identified as part of structurally conserved regions in proteins. This is supported by similar values for the local RMS deviations of the aligned segments for the structural classes of PPII-helices, alpha-helices, and beta-strands. The PPII-helices are shown to participate in supersecondary elements such as PPII-helix/alpha-helix. The conservation of PPII-helices depends on the conservation of a supersecondary element as a whole. PPII-helices also form links, possibly flexible, in the interdomain regions. The role of the PPII-helices in model building by homology is 2-fold; they serve as additional conserved elements in the structure allowing improvement of the accuracy of a model and provide correct chain geometry for modeling of the segments equivalenced to them in a target sequence. The improvement in model building is demonstrated in 2 test studies.

Full Text

The Full Text of this article is available as a PDF (2.9 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adzhubei A. A., Eisenmenger F., Tumanyan V. G., Zinke M., Brodzinski S., Esipova N. G. Third type of secondary structure: noncooperative mobile conformation. Protein Data Bank analysis. Biochem Biophys Res Commun. 1987 Aug 14;146(3):934–938. doi: 10.1016/0006-291x(87)90736-4. [DOI] [PubMed] [Google Scholar]
  2. Adzhubei A. A., Sternberg M. J. Left-handed polyproline II helices commonly occur in globular proteins. J Mol Biol. 1993 Jan 20;229(2):472–493. doi: 10.1006/jmbi.1993.1047. [DOI] [PubMed] [Google Scholar]
  3. Aizenkhaber F., Adzhubei A. A., Aizenmenger F., Esipova N. G. Gidratsiia levoi spirali tipa poli-L-prolin. II. Issledovanie metodom Monte Karlo. Biofizika. 1992 Jan-Feb;37(1):62–67. [PubMed] [Google Scholar]
  4. Ananthanarayanan V. S., Soman K. V., Ramakrishnan C. A novel supersecondary structure in globular proteins comprising the collagen-like helix and beta-turn. J Mol Biol. 1987 Dec 20;198(4):705–709. doi: 10.1016/0022-2836(87)90211-7. [DOI] [PubMed] [Google Scholar]
  5. Arnott S., Dover S. D. The structure of poly-L-proline II. Acta Crystallogr B. 1968 Apr 15;24(4):599–601. doi: 10.1107/s056774086800289x. [DOI] [PubMed] [Google Scholar]
  6. Barton G. J., Sternberg M. J. Evaluation and improvements in the automatic alignment of protein sequences. Protein Eng. 1987 Feb-Mar;1(2):89–94. doi: 10.1093/protein/1.2.89. [DOI] [PubMed] [Google Scholar]
  7. Bartunik H. D., Summers L. J., Bartsch H. H. Crystal structure of bovine beta-trypsin at 1.5 A resolution in a crystal form with low molecular packing density. Active site geometry, ion pairs and solvent structure. J Mol Biol. 1989 Dec 20;210(4):813–828. doi: 10.1016/0022-2836(89)90110-1. [DOI] [PubMed] [Google Scholar]
  8. Bernstein F. C., Koetzle T. F., Williams G. J., Meyer E. F., Jr, Brice M. D., Rodgers J. R., Kennard O., Shimanouchi T., Tasumi M. The Protein Data Bank: a computer-based archival file for macromolecular structures. J Mol Biol. 1977 May 25;112(3):535–542. doi: 10.1016/s0022-2836(77)80200-3. [DOI] [PubMed] [Google Scholar]
  9. Blundell T. L., Johnson M. S. Catching a common fold. Protein Sci. 1993 Jun;2(6):877–883. doi: 10.1002/pro.5560020602. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Blundell T. L., Sibanda B. L., Sternberg M. J., Thornton J. M. Knowledge-based prediction of protein structures and the design of novel molecules. 1987 Mar 26-Apr 1Nature. 326(6111):347–352. doi: 10.1038/326347a0. [DOI] [PubMed] [Google Scholar]
  11. Bode W., Chen Z., Bartels K., Kutzbach C., Schmidt-Kastner G., Bartunik H. Refined 2 A X-ray crystal structure of porcine pancreatic kallikrein A, a specific trypsin-like serine proteinase. Crystallization, structure determination, crystallographic refinement, structure and its comparison with bovine trypsin. J Mol Biol. 1983 Feb 25;164(2):237–282. doi: 10.1016/0022-2836(83)90077-3. [DOI] [PubMed] [Google Scholar]
  12. Chothia C., Lesk A. M. The relation between the divergence of sequence and structure in proteins. EMBO J. 1986 Apr;5(4):823–826. doi: 10.1002/j.1460-2075.1986.tb04288.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Cooper J. B., Khan G., Taylor G., Tickle I. J., Blundell T. L. X-ray analyses of aspartic proteinases. II. Three-dimensional structure of the hexagonal crystal form of porcine pepsin at 2.3 A resolution. J Mol Biol. 1990 Jul 5;214(1):199–222. doi: 10.1016/0022-2836(90)90156-G. [DOI] [PubMed] [Google Scholar]
  14. Deisenhofer J. Crystallographic refinement and atomic models of a human Fc fragment and its complex with fragment B of protein A from Staphylococcus aureus at 2.9- and 2.8-A resolution. Biochemistry. 1981 Apr 28;20(9):2361–2370. [PubMed] [Google Scholar]
  15. Fermi G., Perutz M. F., Shaanan B., Fourme R. The crystal structure of human deoxyhaemoglobin at 1.74 A resolution. J Mol Biol. 1984 May 15;175(2):159–174. doi: 10.1016/0022-2836(84)90472-8. [DOI] [PubMed] [Google Scholar]
  16. Flores T. P., Orengo C. A., Moss D. S., Thornton J. M. Comparison of conformational characteristics in structurally similar protein pairs. Protein Sci. 1993 Nov;2(11):1811–1826. doi: 10.1002/pro.5560021104. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Fujinaga M., Delbaere L. T., Brayer G. D., James M. N. Refined structure of alpha-lytic protease at 1.7 A resolution. Analysis of hydrogen bonding and solvent structure. J Mol Biol. 1985 Aug 5;184(3):479–502. doi: 10.1016/0022-2836(85)90296-7. [DOI] [PubMed] [Google Scholar]
  18. Fujinaga M., James M. N. Rat submaxillary gland serine protease, tonin. Structure solution and refinement at 1.8 A resolution. J Mol Biol. 1987 May 20;195(2):373–396. doi: 10.1016/0022-2836(87)90658-9. [DOI] [PubMed] [Google Scholar]
  19. Gilliland G. L., Winborne E. L., Nachman J., Wlodawer A. The three-dimensional structure of recombinant bovine chymosin at 2.3 A resolution. Proteins. 1990;8(1):82–101. doi: 10.1002/prot.340080110. [DOI] [PubMed] [Google Scholar]
  20. Greer J. Comparative model-building of the mammalian serine proteases. J Mol Biol. 1981 Dec 25;153(4):1027–1042. doi: 10.1016/0022-2836(81)90465-4. [DOI] [PubMed] [Google Scholar]
  21. Hilbert M., Böhm G., Jaenicke R. Structural relationships of homologous proteins as a fundamental principle in homology modeling. Proteins. 1993 Oct;17(2):138–151. doi: 10.1002/prot.340170204. [DOI] [PubMed] [Google Scholar]
  22. Holm L., Ouzounis C., Sander C., Tuparev G., Vriend G. A database of protein structure families with common folding motifs. Protein Sci. 1992 Dec;1(12):1691–1698. doi: 10.1002/pro.5560011217. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. James M. N., Sielecki A. R. Structure and refinement of penicillopepsin at 1.8 A resolution. J Mol Biol. 1983 Jan 15;163(2):299–361. doi: 10.1016/0022-2836(83)90008-6. [DOI] [PubMed] [Google Scholar]
  24. Jones T. A., Thirup S. Using known substructures in protein model building and crystallography. EMBO J. 1986 Apr;5(4):819–822. doi: 10.1002/j.1460-2075.1986.tb04287.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Kabsch W., Sander C. Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features. Biopolymers. 1983 Dec;22(12):2577–2637. doi: 10.1002/bip.360221211. [DOI] [PubMed] [Google Scholar]
  26. Kessler H., Mronga S., Müller G., Moroder L., Huber R. Conformational analysis of a IgG1 hinge peptide derivative in solution determined by NMR spectroscopy and refined by restrained molecular dynamics simulations. Biopolymers. 1991 Sep;31(10):1189–1204. doi: 10.1002/bip.360311007. [DOI] [PubMed] [Google Scholar]
  27. Lesk A. M., Chothia C. How different amino acid sequences determine similar protein structures: the structure and evolutionary dynamics of the globins. J Mol Biol. 1980 Jan 25;136(3):225–270. doi: 10.1016/0022-2836(80)90373-3. [DOI] [PubMed] [Google Scholar]
  28. Lim W. A., Richards F. M. Critical residues in an SH3 domain from Sem-5 suggest a mechanism for proline-rich peptide recognition. Nat Struct Biol. 1994 Apr;1(4):221–225. doi: 10.1038/nsb0494-221. [DOI] [PubMed] [Google Scholar]
  29. Madden D. R., Gorga J. C., Strominger J. L., Wiley D. C. The three-dimensional structure of HLA-B27 at 2.1 A resolution suggests a general mechanism for tight peptide binding to MHC. Cell. 1992 Sep 18;70(6):1035–1048. doi: 10.1016/0092-8674(92)90252-8. [DOI] [PubMed] [Google Scholar]
  30. Makarov A. A., Lobachov V. M., Adzhubei I. A., Esipova N. G. Natural polypeptides in left-handed helical conformation. A circular dichroism study of the linker histones' C-terminal fragments and beta-endorphin. FEBS Lett. 1992 Jul 13;306(1):63–65. doi: 10.1016/0014-5793(92)80838-8. [DOI] [PubMed] [Google Scholar]
  31. Marquart M., Deisenhofer J., Huber R., Palm W. Crystallographic refinement and atomic models of the intact immunoglobulin molecule Kol and its antigen-binding fragment at 3.0 A and 1.0 A resolution. J Mol Biol. 1980 Aug 25;141(4):369–391. doi: 10.1016/0022-2836(80)90252-1. [DOI] [PubMed] [Google Scholar]
  32. Mauguen Y., Hartley R. W., Dodson E. J., Dodson G. G., Bricogne G., Chothia C., Jack A. Molecular structure of a new family of ribonucleases. Nature. 1982 May 13;297(5862):162–164. doi: 10.1038/297162a0. [DOI] [PubMed] [Google Scholar]
  33. Meyer E., Cole G., Radhakrishnan R., Epp O. Structure of native porcine pancreatic elastase at 1.65 A resolutions. Acta Crystallogr B. 1988 Feb 1;44(Pt 1):26–38. doi: 10.1107/s0108768187007559. [DOI] [PubMed] [Google Scholar]
  34. Miller M., Schneider J., Sathyanarayana B. K., Toth M. V., Marshall G. R., Clawson L., Selk L., Kent S. B., Wlodawer A. Structure of complex of synthetic HIV-1 protease with a substrate-based inhibitor at 2.3 A resolution. Science. 1989 Dec 1;246(4934):1149–1152. doi: 10.1126/science.2686029. [DOI] [PubMed] [Google Scholar]
  35. Moult J., Sussman F., James M. N. Electron density calculations as an extension of protein structure refinement. Streptomyces griseus protease A at 1.5 A resolution. J Mol Biol. 1985 Apr 20;182(4):555–566. doi: 10.1016/0022-2836(85)90241-4. [DOI] [PubMed] [Google Scholar]
  36. Navia M. A., McKeever B. M., Springer J. P., Lin T. Y., Williams H. R., Fluder E. M., Dorn C. P., Hoogsteen K. Structure of human neutrophil elastase in complex with a peptide chloromethyl ketone inhibitor at 1.84-A resolution. Proc Natl Acad Sci U S A. 1989 Jan;86(1):7–11. doi: 10.1073/pnas.86.1.7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Orengo C. A., Flores T. P., Taylor W. R., Thornton J. M. Identification and classification of protein fold families. Protein Eng. 1993 Jul;6(5):485–500. doi: 10.1093/protein/6.5.485. [DOI] [PubMed] [Google Scholar]
  38. Pearl L., Blundell T. The active site of aspartic proteinases. FEBS Lett. 1984 Aug 20;174(1):96–101. doi: 10.1016/0014-5793(84)81085-6. [DOI] [PubMed] [Google Scholar]
  39. Perutz M. F., Miurhead H., Cox J. M., Goaman L. C., Mathews F. S., McGandy E. L., Webb L. E. Three-dimensional Fourier synthesis of horse oxyhaemoglobin at 2.8 A resolution: (1) x-ray analysis. Nature. 1968 Jul 6;219(5149):29–32. doi: 10.1038/219029a0. [DOI] [PubMed] [Google Scholar]
  40. Pickett S. D., Saqi M. A., Sternberg M. J. Evaluation of the sequence template method for protein structure prediction. Discrimination of the (beta/alpha)8-barrel fold. J Mol Biol. 1992 Nov 5;228(1):170–187. doi: 10.1016/0022-2836(92)90499-a. [DOI] [PubMed] [Google Scholar]
  41. Read R. J., James M. N. Refined crystal structure of Streptomyces griseus trypsin at 1.7 A resolution. J Mol Biol. 1988 Apr 5;200(3):523–551. doi: 10.1016/0022-2836(88)90541-4. [DOI] [PubMed] [Google Scholar]
  42. Remington S. J., Woodbury R. G., Reynolds R. A., Matthews B. W., Neurath H. The structure of rat mast cell protease II at 1.9-A resolution. Biochemistry. 1988 Oct 18;27(21):8097–8105. doi: 10.1021/bi00421a019. [DOI] [PubMed] [Google Scholar]
  43. Richards F. M., Kundrot C. E. Identification of structural motifs from protein coordinate data: secondary structure and first-level supersecondary structure. Proteins. 1988;3(2):71–84. doi: 10.1002/prot.340030202. [DOI] [PubMed] [Google Scholar]
  44. Siligardi G., Drake A. F., Mascagni P., Rowlands D., Brown F., Gibbons W. A. Correlations between the conformations elucidated by CD spectroscopy and the antigenic properties of four peptides of the foot-and-mouth disease virus. Eur J Biochem. 1991 Aug 1;199(3):545–551. doi: 10.1111/j.1432-1033.1991.tb16153.x. [DOI] [PubMed] [Google Scholar]
  45. Sklenar H., Etchebest C., Lavery R. Describing protein structure: a general algorithm yielding complete helicoidal parameters and a unique overall axis. Proteins. 1989;6(1):46–60. doi: 10.1002/prot.340060105. [DOI] [PubMed] [Google Scholar]
  46. Sreerama N., Woody R. W. Poly(pro)II helices in globular proteins: identification and circular dichroic analysis. Biochemistry. 1994 Aug 23;33(33):10022–10025. doi: 10.1021/bi00199a028. [DOI] [PubMed] [Google Scholar]
  47. Subramanian E., Swan I. D., Liu M., Davies D. R., Jenkins J. A., Tickle I. J., Blundell T. L. Homology among acid proteases: comparison of crystal structures at 3A resolution of acid proteases from Rhizopus chinensis and Endothia parasitica. Proc Natl Acad Sci U S A. 1977 Feb;74(2):556–559. doi: 10.1073/pnas.74.2.556. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Suguna K., Bott R. R., Padlan E. A., Subramanian E., Sheriff S., Cohen G. H., Davies D. R. Structure and refinement at 1.8 A resolution of the aspartic proteinase from Rhizopus chinensis. J Mol Biol. 1987 Aug 20;196(4):877–900. doi: 10.1016/0022-2836(87)90411-6. [DOI] [PubMed] [Google Scholar]
  49. Sutcliffe M. J., Haneef I., Carney D., Blundell T. L. Knowledge based modelling of homologous proteins, Part I: Three-dimensional frameworks derived from the simultaneous superposition of multiple structures. Protein Eng. 1987 Oct-Nov;1(5):377–384. doi: 10.1093/protein/1.5.377. [DOI] [PubMed] [Google Scholar]
  50. Sutcliffe M. J., Hayes F. R., Blundell T. L. Knowledge based modelling of homologous proteins, Part II: Rules for the conformations of substituted sidechains. Protein Eng. 1987 Oct-Nov;1(5):385–392. doi: 10.1093/protein/1.5.385. [DOI] [PubMed] [Google Scholar]
  51. Taylor W. R., Orengo C. A. A holistic approach to protein structure alignment. Protein Eng. 1989 May;2(7):505–519. doi: 10.1093/protein/2.7.505. [DOI] [PubMed] [Google Scholar]
  52. Taylor W. R., Orengo C. A. Protein structure alignment. J Mol Biol. 1989 Jul 5;208(1):1–22. doi: 10.1016/0022-2836(89)90084-3. [DOI] [PubMed] [Google Scholar]
  53. Tsukada H., Blow D. M. Structure of alpha-chymotrypsin refined at 1.68 A resolution. J Mol Biol. 1985 Aug 20;184(4):703–711. doi: 10.1016/0022-2836(85)90314-6. [DOI] [PubMed] [Google Scholar]
  54. Yee D. P., Dill K. A. Families and the structural relatedness among globular proteins. Protein Sci. 1993 Jun;2(6):884–899. doi: 10.1002/pro.5560020603. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Yu H., Chen J. K., Feng S., Dalgarno D. C., Brauer A. W., Schreiber S. L. Structural basis for the binding of proline-rich peptides to SH3 domains. Cell. 1994 Mar 11;76(5):933–945. doi: 10.1016/0092-8674(94)90367-0. [DOI] [PubMed] [Google Scholar]

Articles from Protein Science : A Publication of the Protein Society are provided here courtesy of The Protein Society

RESOURCES