Computational and Structural Characterisation of Protein Associations

  • Susan Jones
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 747)

Abstract

Protein-protein associations represent the building blocks of biological systems. The classification of different types of protein association is fundamental to an understanding of the interactions they exhibit. A protein association can be classified as homo- (identical components) or hetero- (non-identical components) and in addition permanent (components only exist and function in an associated state) or transient (components exist independently but interact for a limited time to carry out a specific function). A large number of studies have analysed the physical and chemical characteristics of protein-protein interactions using three-dimensional structures derived from X-ray crystallography. This chapter summarises the major conclusions of these studies, focusing on amino acid preferences and secondary structure packing at interfaces: hydration, hydrophobic and electrostatic effects, conformational changes and evolutionary conservation. The studies highlight differences between the interaction sites and the rest of the protein surface and between different classes of protein association. Common themes in the interfaces of protein associations are also revealed including shape complementarity, the presence of water molecules, a high percentage of arginine residues, intermolecular hydrogen bonds and an energy of association comprising hydrophobic and electrostatic effects. These studies also emphasise how the relative importance of such characteristics is dependant upon the class of protein association, with permanent associations generally displaying different characteristics to transient associations.

Keywords

Hydration Tyrosine Influenza Lysin Oligomerization 

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References

  1. 1.
    Berman HM et al. The protein data bank. Nucleic Acids Res 2000; 28(1):235–242.PubMedCrossRefGoogle Scholar
  2. 2.
    Jones S, Thornton JM. Principles of protein-protein interactions. Proc Natl Acad Sci USA 1996; 93(1):13–20.PubMedCrossRefGoogle Scholar
  3. 3.
    Nooren IMA, Thornton JM. Diversity of protein-protein interactions. EMBO J 2003; 22(14):3486–3492.PubMedCrossRefGoogle Scholar
  4. 4.
    De S et al. Interaction preferences across protein-protein interfaces of obligatory and non-obligatory components are different. BMC Struct Biol 2005; 5.Google Scholar
  5. 5.
    Ansari S, Helms V. Statistical analysis of predominantly transient protein-protein interfaces. Proteins 2005; 61(2):344–355.PubMedCrossRefGoogle Scholar
  6. 6.
    Ofran Y, Rost B. Analysing six types of protein-protein interfaces. J Mol Biol 2003; 325(2):377–387.PubMedCrossRefGoogle Scholar
  7. 7.
    Ponstingl H, Kabir T, Thornton JM. Automatic inference of protein quaternary structure from crystals. J Appl Crystallogr 2003; 36:1116–1122.CrossRefGoogle Scholar
  8. 8.
    Bahadur RP et al. A dissection of specific and nonspecific protein—Protein interfaces. J Mol Biol 2004; 336(4):943–955.PubMedCrossRefGoogle Scholar
  9. 9.
    Henrick K, Thornton JM. PQS: a protein quaternary structure file server. Trends Biochem Sci 1998; 23(9):358–361.PubMedCrossRefGoogle Scholar
  10. 10.
    Chothia C, Janin J. Principles of Protein-Protein Recognition. Nature 1975; 256(5520):705–708.PubMedCrossRefGoogle Scholar
  11. 11.
    Janin J, Miller S, Chothia C. Surface, Subunit Interfaces and Interior of Oligomeric Proteins. J Mol Biol 1988; 204(1):155–164.PubMedCrossRefGoogle Scholar
  12. 12.
    Miller S. The structure of interfaces between subunits of dimeric and tetrameric proteins. Protein Eng 1989; 3(2):77–83.PubMedCrossRefGoogle Scholar
  13. 13.
    Lo Conte L, Chothia C, Janin J. The atomic structure of protein-protein recognition sites. J Mol Biol 1999; 285(5):2177–2198.PubMedCrossRefGoogle Scholar
  14. 14.
    Jones S, Thornton JM, Protein-protein interactions—a review of protein dimer structures. Prog Biophys Mol Biol 1995; 63(1):13–20.CrossRefGoogle Scholar
  15. 15.
    Ponstingl H et al. Morphological aspects of oligorneric protein structures. Prog Biophys Mol Biol 2005; 89(1):9–35.PubMedCrossRefGoogle Scholar
  16. 16.
    Bordner AJ, Abagyan R. Statistical analysis and prediction of protein-protein interfaces. Proteins 2005; 60(3):353–366.PubMedCrossRefGoogle Scholar
  17. 17.
    Bogan AA, Thorn KS. Anatomy of hot spots in protein interfaces. J Mol Biol 1998; 280(1):1–9.PubMedCrossRefGoogle Scholar
  18. 18.
    Glaser F et al. Residue frequencies and pairing preferences at protein-protein interfaces. Proteins 2001; 43(2):89–102.PubMedCrossRefGoogle Scholar
  19. 19.
    Chakrabarti P, Janin J. Dissecting protein-protein recognition sites. Proteins 2002; 47(3):334–343.PubMedCrossRefGoogle Scholar
  20. 20.
    Chothia C. Nature of accessible and buried surfaces in proteins. J Mol Biol 1976; 105(1):1–14.PubMedCrossRefGoogle Scholar
  21. 21.
    Jones S, Thornton JM. Analysis of protein-protein interaction sites using surface patches. J Mol Biol 1997; 272(1):121–132.PubMedCrossRefGoogle Scholar
  22. 22.
    Sheinerman FB, Norel R, Honig B. Electrostatic aspects of protein-protein interactions. Curr Opin Struct Biol 2000; 10(2):153–159.PubMedCrossRefGoogle Scholar
  23. 23.
    Bahar I, Jernigan RL. Inter-residue potentials in globular proteins and the dominance of highly specific hydrophilic interactions at close separation. J Mol Biol 1997; 266(1):195–214.PubMedCrossRefGoogle Scholar
  24. 24.
    Zhou HX, Shan YB. Prediction of protein interaction sites from sequence profile and residue neighbor list. Proteins 2001; 44(3):336–343.PubMedCrossRefGoogle Scholar
  25. 25.
    Nooren IMA, Thornton JM. Structural characterisation and functional significance of transient protein-protein interactions. J Mol Biol 2003; 325(5):991–1018.PubMedCrossRefGoogle Scholar
  26. 26.
    Jiang SL, Tovchigrechko A, Vakser IA. The role of geometric complementarity in secondary structure packing: A systematic docking study. Protein Sci 2003; 12(8):1646–1651.PubMedCrossRefGoogle Scholar
  27. 27.
    Rodier F et al. Hydration of protein-protein interfaces. Proteins 2005; 60(1):36–45.PubMedCrossRefGoogle Scholar
  28. 28.
    Monecke P et al. Determination of the interfacial water content in protein-protein complexes from free energy simulations. Biophys J 2006; 90(3):841–850.PubMedCrossRefGoogle Scholar
  29. 29.
    Janin J. Wet and dry interfaces: the role of solvent in protein-protein and protein-DNA recognition. Structure with Fold Des 1999; 7(12):R277–R279.CrossRefGoogle Scholar
  30. 30.
    Hubbard SJ, Argos P. Cavities and packing at protein interfaces. Protein Sci 1994; 3(12):2194–2206.PubMedCrossRefGoogle Scholar
  31. 31.
    Kauzmann W. Some factors in the interpretation of protein denaturation. Adv Protein Chem 1959; 14:1–63.PubMedCrossRefGoogle Scholar
  32. 32.
    Dill KA. Dominant forces in protein folding. Biochemistry 1990; 29(31):7133–7155.PubMedCrossRefGoogle Scholar
  33. 33.
    Xu D, Lin SL, Nussinov R. Protein binding versus protein folding: The role of hydrophilic bridges in protein associations. J Mol Biol 1997; 265(1):68–84.PubMedCrossRefGoogle Scholar
  34. 34.
    Tsai CJ et al. Studies of protein-protein interfaces: A statistical analysis of the hydrophobic effect. Protein Sci 1997; 6(1):53–64.PubMedCrossRefGoogle Scholar
  35. 35.
    Sundberg EJ et al. Estimation of the hydrophobic effect in an antigen-antibody protein-protein interface. Biochemistry 2000; 39(50):15375–15387.PubMedCrossRefGoogle Scholar
  36. 36.
    Li YL et al. Magnitude of the hydrophobic effect at central versus peripheral sites in protein-protein interfaces. Structure 2005; 13(2):297–307.PubMedCrossRefGoogle Scholar
  37. 37.
    Ratnaparkhi GS, Varadarajan R. Thermodynamic and structural studies of cavity formation in proteins suggest that loss of packing interactions rather than the hydrophobic effect dominates the observed energetics. Biochemistry 2000; 39(40):12365–12374.PubMedCrossRefGoogle Scholar
  38. 38.
    Sheinerman FB, Honig B. On the role of electrostatic interactions in the design of protein-protein interfaces. J Mol Biol 2002; 318(1):161–177.PubMedCrossRefGoogle Scholar
  39. 39.
    Froloff N, Windemuth A, Honig B. On the calculation of binding free energies using continuum methods: Application to MHC class I protein-peptide interactions. Protein Sci 1997; 6(6):1293–1301.PubMedCrossRefGoogle Scholar
  40. 40.
    Schapira M, Totrov M, Abagyan R. Prediction of the binding energy for small molecules, peptides and proteins. J Mol Recognit 1999; 12(3):177–190.PubMedCrossRefGoogle Scholar
  41. 41.
    Hendsch ZS, Tidor B. Do salt bridges stabilize proteins—a continuum electrostatic analysis. Protein Sci 1994; 3(2):211–226.PubMedCrossRefGoogle Scholar
  42. 42.
    Kortemme T, Baker D. A simple physical model for binding energy hot spots in protein-protein complexes. Proc Natl Acad Sci USA 2002; 99(22):14116–14121.PubMedCrossRefGoogle Scholar
  43. 43.
    Janin J, Chothia C. The structure of protein-protein recognition sites. J Biol Chem 1990; 265(27):16027–16030.PubMedGoogle Scholar
  44. 44.
    Echols N, Milburn D, Gerstein M. MolMovDB: analysis and visualization of conformational change and structural flexibility. Nucleic Acids Res 2003; 31(1):478–482.PubMedCrossRefGoogle Scholar
  45. 45.
    Betts MJ, Sternberg MJE. An analysis of conformational changes on protein-protein association: implications for predictive docking. Protein Eng 1999; 12(4):271–283.PubMedCrossRefGoogle Scholar
  46. 46.
    Schneider TR. Objective comparison of protein structures: error-scaled difference distance matrices. Acta Crystallogr D Biol Crystallogr 2000; 56:714–721.PubMedCrossRefGoogle Scholar
  47. 47.
    Ji ZL et al. KDBI: Kinetic Data of Bio-molecular Interactions Database. Nucleic Acids Res 2003; 31:255–257.PubMedCrossRefGoogle Scholar
  48. 48.
    Kumar MDS, Gromiha MM. PINT: Protein-protein interactions thermodynamic database. Nucleic Acids Res 2006; 34:D195–D198.PubMedCrossRefGoogle Scholar
  49. 49.
    Grishin NV, Phillips MA. The subunit interfaces of oligomeric enzymes are conserved to a similar extent to the overall protein sequences. Protein Sci 1994; 3(12):2455–2458.PubMedCrossRefGoogle Scholar
  50. 50.
    Valdar WSJ, Thornton JM. Protein-protein interfaces: Analysis of amino acid conservation in homodimers. Proteins 2001; 42(1):108–124.PubMedCrossRefGoogle Scholar
  51. 51.
    Caffrey DR et al. Are protein-protein interfaces more conserved in sequence than the rest of the protein surface? Protein Sci 2004; 13(1):190–202.PubMedCrossRefGoogle Scholar
  52. 52.
    Rees B et al. Cardiotoxin-V4ii from Naja-Mossambica-Mossambica—the refined crystal-structure. J Mol Biol 1990; 214(1):281–297.PubMedCrossRefGoogle Scholar
  53. 53.
    Lapthorn AJ et al. Crystal-structure of human chorionic-gonadotropin. Nature 1994; 369(6480):455–461.PubMedCrossRefGoogle Scholar
  54. 54.
    Kresge N, Vacquier VD, Stout CD. 1.35 and 2.07 angstrom resolution structures of the red abalone sperm lysin monomer and dimer reveal features involved in receptor binding. Acta Crystallogr D Biol Crystallogr 2000; 56:34–41.PubMedCrossRefGoogle Scholar
  55. 55.
    Kawashima T et al. The structure of the Escherichia coli EF-Tu center dot EF-Ts complex at 2.5 angstrom resolution. Nature 1996; 379(6565):511–518.PubMedCrossRefGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2012

Authors and Affiliations

  • Susan Jones
    • 1
  1. 1.Department of Biochemistry, School of Life SciencesUniversity of SussexBrightonUK

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