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.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Berman HM et al. The protein data bank. Nucleic Acids Res 2000; 28(1):235–242.
Jones S, Thornton JM. Principles of protein-protein interactions. Proc Natl Acad Sci USA 1996; 93(1):13–20.
Nooren IMA, Thornton JM. Diversity of protein-protein interactions. EMBO J 2003; 22(14):3486–3492.
De S et al. Interaction preferences across protein-protein interfaces of obligatory and non-obligatory components are different. BMC Struct Biol 2005; 5.
Ansari S, Helms V. Statistical analysis of predominantly transient protein-protein interfaces. Proteins 2005; 61(2):344–355.
Ofran Y, Rost B. Analysing six types of protein-protein interfaces. J Mol Biol 2003; 325(2):377–387.
Ponstingl H, Kabir T, Thornton JM. Automatic inference of protein quaternary structure from crystals. J Appl Crystallogr 2003; 36:1116–1122.
Bahadur RP et al. A dissection of specific and nonspecific protein—Protein interfaces. J Mol Biol 2004; 336(4):943–955.
Henrick K, Thornton JM. PQS: a protein quaternary structure file server. Trends Biochem Sci 1998; 23(9):358–361.
Chothia C, Janin J. Principles of Protein-Protein Recognition. Nature 1975; 256(5520):705–708.
Janin J, Miller S, Chothia C. Surface, Subunit Interfaces and Interior of Oligomeric Proteins. J Mol Biol 1988; 204(1):155–164.
Miller S. The structure of interfaces between subunits of dimeric and tetrameric proteins. Protein Eng 1989; 3(2):77–83.
Lo Conte L, Chothia C, Janin J. The atomic structure of protein-protein recognition sites. J Mol Biol 1999; 285(5):2177–2198.
Jones S, Thornton JM, Protein-protein interactions—a review of protein dimer structures. Prog Biophys Mol Biol 1995; 63(1):13–20.
Ponstingl H et al. Morphological aspects of oligorneric protein structures. Prog Biophys Mol Biol 2005; 89(1):9–35.
Bordner AJ, Abagyan R. Statistical analysis and prediction of protein-protein interfaces. Proteins 2005; 60(3):353–366.
Bogan AA, Thorn KS. Anatomy of hot spots in protein interfaces. J Mol Biol 1998; 280(1):1–9.
Glaser F et al. Residue frequencies and pairing preferences at protein-protein interfaces. Proteins 2001; 43(2):89–102.
Chakrabarti P, Janin J. Dissecting protein-protein recognition sites. Proteins 2002; 47(3):334–343.
Chothia C. Nature of accessible and buried surfaces in proteins. J Mol Biol 1976; 105(1):1–14.
Jones S, Thornton JM. Analysis of protein-protein interaction sites using surface patches. J Mol Biol 1997; 272(1):121–132.
Sheinerman FB, Norel R, Honig B. Electrostatic aspects of protein-protein interactions. Curr Opin Struct Biol 2000; 10(2):153–159.
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.
Zhou HX, Shan YB. Prediction of protein interaction sites from sequence profile and residue neighbor list. Proteins 2001; 44(3):336–343.
Nooren IMA, Thornton JM. Structural characterisation and functional significance of transient protein-protein interactions. J Mol Biol 2003; 325(5):991–1018.
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.
Rodier F et al. Hydration of protein-protein interfaces. Proteins 2005; 60(1):36–45.
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.
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.
Hubbard SJ, Argos P. Cavities and packing at protein interfaces. Protein Sci 1994; 3(12):2194–2206.
Kauzmann W. Some factors in the interpretation of protein denaturation. Adv Protein Chem 1959; 14:1–63.
Dill KA. Dominant forces in protein folding. Biochemistry 1990; 29(31):7133–7155.
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.
Tsai CJ et al. Studies of protein-protein interfaces: A statistical analysis of the hydrophobic effect. Protein Sci 1997; 6(1):53–64.
Sundberg EJ et al. Estimation of the hydrophobic effect in an antigen-antibody protein-protein interface. Biochemistry 2000; 39(50):15375–15387.
Li YL et al. Magnitude of the hydrophobic effect at central versus peripheral sites in protein-protein interfaces. Structure 2005; 13(2):297–307.
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.
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.
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.
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.
Hendsch ZS, Tidor B. Do salt bridges stabilize proteins—a continuum electrostatic analysis. Protein Sci 1994; 3(2):211–226.
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.
Janin J, Chothia C. The structure of protein-protein recognition sites. J Biol Chem 1990; 265(27):16027–16030.
Echols N, Milburn D, Gerstein M. MolMovDB: analysis and visualization of conformational change and structural flexibility. Nucleic Acids Res 2003; 31(1):478–482.
Betts MJ, Sternberg MJE. An analysis of conformational changes on protein-protein association: implications for predictive docking. Protein Eng 1999; 12(4):271–283.
Schneider TR. Objective comparison of protein structures: error-scaled difference distance matrices. Acta Crystallogr D Biol Crystallogr 2000; 56:714–721.
Ji ZL et al. KDBI: Kinetic Data of Bio-molecular Interactions Database. Nucleic Acids Res 2003; 31:255–257.
Kumar MDS, Gromiha MM. PINT: Protein-protein interactions thermodynamic database. Nucleic Acids Res 2006; 34:D195–D198.
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.
Valdar WSJ, Thornton JM. Protein-protein interfaces: Analysis of amino acid conservation in homodimers. Proteins 2001; 42(1):108–124.
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.
Rees B et al. Cardiotoxin-V4ii from Naja-Mossambica-Mossambica—the refined crystal-structure. J Mol Biol 1990; 214(1):281–297.
Lapthorn AJ et al. Crystal-structure of human chorionic-gonadotropin. Nature 1994; 369(6480):455–461.
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.
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.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Landes Bioscience and Springer Science+Business Media
About this chapter
Cite this chapter
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
Download citation
DOI: https://doi.org/10.1007/978-1-4614-3229-6_3
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4614-3228-9
Online ISBN: 978-1-4614-3229-6
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)