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Computational and Structural Characterisation of Protein Associations

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Protein Dimerization and Oligomerization in Biology

Part of the book series: Advances in Experimental Medicine and Biology ((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.

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References

  1. Berman HM et al. The protein data bank. Nucleic Acids Res 2000; 28(1):235–242.

    Article  PubMed  CAS  Google Scholar 

  2. Jones S, Thornton JM. Principles of protein-protein interactions. Proc Natl Acad Sci USA 1996; 93(1):13–20.

    Article  PubMed  CAS  Google Scholar 

  3. Nooren IMA, Thornton JM. Diversity of protein-protein interactions. EMBO J 2003; 22(14):3486–3492.

    Article  PubMed  CAS  Google Scholar 

  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. Ansari S, Helms V. Statistical analysis of predominantly transient protein-protein interfaces. Proteins 2005; 61(2):344–355.

    Article  PubMed  CAS  Google Scholar 

  6. Ofran Y, Rost B. Analysing six types of protein-protein interfaces. J Mol Biol 2003; 325(2):377–387.

    Article  PubMed  CAS  Google Scholar 

  7. Ponstingl H, Kabir T, Thornton JM. Automatic inference of protein quaternary structure from crystals. J Appl Crystallogr 2003; 36:1116–1122.

    Article  CAS  Google Scholar 

  8. Bahadur RP et al. A dissection of specific and nonspecific protein—Protein interfaces. J Mol Biol 2004; 336(4):943–955.

    Article  PubMed  CAS  Google Scholar 

  9. Henrick K, Thornton JM. PQS: a protein quaternary structure file server. Trends Biochem Sci 1998; 23(9):358–361.

    Article  PubMed  CAS  Google Scholar 

  10. Chothia C, Janin J. Principles of Protein-Protein Recognition. Nature 1975; 256(5520):705–708.

    Article  PubMed  CAS  Google Scholar 

  11. Janin J, Miller S, Chothia C. Surface, Subunit Interfaces and Interior of Oligomeric Proteins. J Mol Biol 1988; 204(1):155–164.

    Article  PubMed  CAS  Google Scholar 

  12. Miller S. The structure of interfaces between subunits of dimeric and tetrameric proteins. Protein Eng 1989; 3(2):77–83.

    Article  PubMed  CAS  Google Scholar 

  13. Lo Conte L, Chothia C, Janin J. The atomic structure of protein-protein recognition sites. J Mol Biol 1999; 285(5):2177–2198.

    Article  PubMed  Google Scholar 

  14. Jones S, Thornton JM, Protein-protein interactions—a review of protein dimer structures. Prog Biophys Mol Biol 1995; 63(1):13–20.

    Article  Google Scholar 

  15. Ponstingl H et al. Morphological aspects of oligorneric protein structures. Prog Biophys Mol Biol 2005; 89(1):9–35.

    Article  PubMed  CAS  Google Scholar 

  16. Bordner AJ, Abagyan R. Statistical analysis and prediction of protein-protein interfaces. Proteins 2005; 60(3):353–366.

    Article  PubMed  CAS  Google Scholar 

  17. Bogan AA, Thorn KS. Anatomy of hot spots in protein interfaces. J Mol Biol 1998; 280(1):1–9.

    Article  PubMed  CAS  Google Scholar 

  18. Glaser F et al. Residue frequencies and pairing preferences at protein-protein interfaces. Proteins 2001; 43(2):89–102.

    Article  PubMed  CAS  Google Scholar 

  19. Chakrabarti P, Janin J. Dissecting protein-protein recognition sites. Proteins 2002; 47(3):334–343.

    Article  PubMed  CAS  Google Scholar 

  20. Chothia C. Nature of accessible and buried surfaces in proteins. J Mol Biol 1976; 105(1):1–14.

    Article  PubMed  CAS  Google Scholar 

  21. Jones S, Thornton JM. Analysis of protein-protein interaction sites using surface patches. J Mol Biol 1997; 272(1):121–132.

    Article  PubMed  CAS  Google Scholar 

  22. Sheinerman FB, Norel R, Honig B. Electrostatic aspects of protein-protein interactions. Curr Opin Struct Biol 2000; 10(2):153–159.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  24. Zhou HX, Shan YB. Prediction of protein interaction sites from sequence profile and residue neighbor list. Proteins 2001; 44(3):336–343.

    Article  PubMed  CAS  Google Scholar 

  25. Nooren IMA, Thornton JM. Structural characterisation and functional significance of transient protein-protein interactions. J Mol Biol 2003; 325(5):991–1018.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  27. Rodier F et al. Hydration of protein-protein interfaces. Proteins 2005; 60(1):36–45.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  30. Hubbard SJ, Argos P. Cavities and packing at protein interfaces. Protein Sci 1994; 3(12):2194–2206.

    Article  PubMed  CAS  Google Scholar 

  31. Kauzmann W. Some factors in the interpretation of protein denaturation. Adv Protein Chem 1959; 14:1–63.

    Article  PubMed  CAS  Google Scholar 

  32. Dill KA. Dominant forces in protein folding. Biochemistry 1990; 29(31):7133–7155.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  34. Tsai CJ et al. Studies of protein-protein interfaces: A statistical analysis of the hydrophobic effect. Protein Sci 1997; 6(1):53–64.

    Article  PubMed  CAS  Google Scholar 

  35. Sundberg EJ et al. Estimation of the hydrophobic effect in an antigen-antibody protein-protein interface. Biochemistry 2000; 39(50):15375–15387.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  41. Hendsch ZS, Tidor B. Do salt bridges stabilize proteins—a continuum electrostatic analysis. Protein Sci 1994; 3(2):211–226.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  43. Janin J, Chothia C. The structure of protein-protein recognition sites. J Biol Chem 1990; 265(27):16027–16030.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  46. Schneider TR. Objective comparison of protein structures: error-scaled difference distance matrices. Acta Crystallogr D Biol Crystallogr 2000; 56:714–721.

    Article  PubMed  CAS  Google Scholar 

  47. Ji ZL et al. KDBI: Kinetic Data of Bio-molecular Interactions Database. Nucleic Acids Res 2003; 31:255–257.

    Article  PubMed  CAS  Google Scholar 

  48. Kumar MDS, Gromiha MM. PINT: Protein-protein interactions thermodynamic database. Nucleic Acids Res 2006; 34:D195–D198.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  50. Valdar WSJ, Thornton JM. Protein-protein interfaces: Analysis of amino acid conservation in homodimers. Proteins 2001; 42(1):108–124.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  52. Rees B et al. Cardiotoxin-V4ii from Naja-Mossambica-Mossambica—the refined crystal-structure. J Mol Biol 1990; 214(1):281–297.

    Article  PubMed  CAS  Google Scholar 

  53. Lapthorn AJ et al. Crystal-structure of human chorionic-gonadotropin. Nature 1994; 369(6480):455–461.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

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Jones, S. (2012). Computational and Structural Characterisation of Protein Associations. In: Matthews, J.M. (eds) Protein Dimerization and Oligomerization in Biology. Advances in Experimental Medicine and Biology, vol 747. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3229-6_3

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