Electrostatic complementarity at protein/protein interfaces.

Calculation of the electrostatic potential of protein-protein complexes has led to the general assertion that protein-protein interfaces display "charge complementarity" and "electrostatic complementarity". In this study, quantitative measures for these two terms are developed and used to investigate protein-protein interfaces in a rigorous manner. Charge complementarity (CC) was defined using the correlation of charges on nearest neighbour atoms at the interface. All 12 protein-protein interfaces studied had insignificantly small CC values. Therefore, the term charge complementarity is not appropriate for the description of protein-protein interfaces when used in the sense measured by CC. Electrostatic complementarity (EC) was defined using the correlation of surface electrostatic potential at protein-protein interfaces. All twelve protein-protein interfaces studied had significant EC values, and thus the assertion that protein-protein association involves surfaces with complementary electrostatic potential was substantially confirmed. The term electrostatic complementarity can therefore be used to describe protein-protein interfaces when used in the sense measured by EC. Taken together, the results for CC and EC demonstrate the relevance of the long-range effects of charges, as described by the electrostatic potential at the binding interface. The EC value did not partition the complexes by type such as antigen-antibody and proteinase-inhibitor, as measures of the geometrical complementarity at protein-protein interfaces have done. The EC value was also not directly related to the number of salt bridges in the interface, and neutralisation of these salt bridges showed that other charges also contributed significantly to electrostatic complementarity and electrostatic interactions between the proteins. Electrostatic complementarity as defined by EC was extended to investigate the electrostatic similarity at the surface of influenza virus neuraminidase where the epitopes of two monoclonal antibodies, NC10 and NC41, overlap. Although NC10 and NC41 both have quite high values of EC for their interaction with neuraminidase, the similarity in electrostatic potential generated by the two on the overlapping region of the epitopes is insignificant. Thus, it is possible for two antibodies to recognise the electrostatic surface of a protein in dissimilar ways.

[1]  G. Air,et al.  Identification of critical contact residues in the NC41 epitope of a subtype N9 influenza virus neuraminidase , 1993, Proteins.

[2]  K. Sharp,et al.  Accurate Calculation of Hydration Free Energies Using Macroscopic Solvent Models , 1994 .

[3]  K. Clauser,et al.  Dimerization of the extracellular domain of the human growth hormone receptor by a single hormone molecule. , 1991, Science.

[4]  D. Osguthorpe,et al.  Structure and energetics of ligand binding to proteins: Escherichia coli dihydrofolate reductase‐trimethoprim, a drug‐receptor system , 1988, Proteins.

[5]  M. Ultsch,et al.  Human growth hormone and extracellular domain of its receptor: crystal structure of the complex. , 1992, Science.

[6]  Alarich Weiss,et al.  Arnold Bondi: Physical Properties of Molecular Crystals, Liquids, and Glasses. John Wiley and Sons, New York, London, Sydney 1968. 502 Seiten. Preis: 175 s. , 1968, Berichte der Bunsengesellschaft für physikalische Chemie.

[7]  A. Gronenborn,et al.  Solution structure of recombinant hirudin and the Lys-47----Glu mutant: a nuclear magnetic resonance and hybrid distance geometry-dynamical simulated annealing study. , 1990, Biochemistry.

[8]  J M Thornton,et al.  Protein-protein interactions: a review of protein dimer structures. , 1995, Progress in biophysics and molecular biology.

[9]  W G Laver,et al.  Refined crystal structure of the influenza virus N9 neuraminidase-NC41 Fab complex. , 1992, Journal of molecular biology.

[10]  J. Hofsteenge,et al.  Use of site-directed mutagenesis to investigate the basis for the specificity of hirudin. , 1988, Biochemistry.

[11]  T. Clackson,et al.  A hot spot of binding energy in a hormone-receptor interface , 1995, Science.

[12]  M J Sternberg,et al.  Application of scaled particle theory to model the hydrophobic effect: implications for molecular association and protein stability. , 1994, Protein engineering.

[13]  W. Bode,et al.  Electrostatic interactions in the association of proteins: An analysis of the thrombin–hirudin complex , 1992, Protein science : a publication of the Protein Society.

[14]  Peter A. Kollman,et al.  Electrostatic recognition between superoxide and copper, zinc superoxide dismutase , 1983, Nature.

[15]  R. Bruccoleri,et al.  On the attribution of binding energy in antigen-antibody complexes McPC 603, D1.3, and HyHEL-5. , 1989, Biochemistry.

[16]  Axel T. Brunger,et al.  X-PLOR Version 3.1: A System for X-ray Crystallography and NMR , 1992 .

[17]  B C Finzel,et al.  Three-dimensional structure of an antibody-antigen complex. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[18]  B. Honig,et al.  A rapid finite difference algorithm, utilizing successive over‐relaxation to solve the Poisson–Boltzmann equation , 1991 .

[19]  Randy J. Read,et al.  Crystal and molecular structures of the complex of α-chymotrypsin with its inhibitor Turkey ovomucoid third domain at 1.8 Å resolution , 1987 .

[20]  H. Wolfson,et al.  Shape complementarity at protein–protein interfaces , 1994, Biopolymers.

[21]  G. Winter,et al.  The contribution of contact and non-contact residues of antibody in the affinity of binding to antigen. The interaction of mutant D1.3 antibodies with lysozyme. , 1993, Journal of molecular biology.

[22]  B. Honig,et al.  On the environment of ionizable groups in globular proteins. , 1984, Journal of molecular biology.

[23]  R. Webster,et al.  N9 neuraminidase complexes with antibodies NC41 and NC10: empirical free energy calculations capture specificity trends observed with mutant binding data. , 1994, Biochemistry.

[24]  L. Pauling.  The Nature Of The Chemical Bond , 1939 .

[25]  B. Honig,et al.  Calculation of the total electrostatic energy of a macromolecular system: Solvation energies, binding energies, and conformational analysis , 1988, Proteins.

[26]  R. Poljak,et al.  Structural features of the reactions between antibodies and protein antigens , 1995, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[27]  B. Honig,et al.  Classical electrostatics in biology and chemistry. , 1995, Science.

[28]  Peter G. Schultz,et al.  The Immunological Evolution of Catalysis , 1996, Science.

[29]  Philip M. Dean,et al.  Electrostatic complementarity between proteins and ligands. 1. Charge disposition, dielectric and interface effects , 1994, J. Comput. Aided Mol. Des..

[30]  G. N. Ramachandran,et al.  Conformation of polypeptides and proteins. , 1968, Advances in protein chemistry.

[31]  A. Bondi,et al.  Physical properties of molecular crystals liquids, and glasses , 1968 .

[32]  M. James,et al.  Crystal and molecular structure of the serine proteinase inhibitor CI-2 from barley seeds. , 1988, Biochemistry.

[33]  M. Pellegrini,et al.  Crystal Structure of a Cross-reaction Complex between Fab F9.13.7 and Guinea Fowl Lysozyme (*) , 1995, The Journal of Biological Chemistry.

[34]  K. Wüthrich,et al.  Conformation of recombinant desulfatohirudin in aqueous solution determined by nuclear magnetic resonance. , 1989, Biochemistry.

[35]  Tom L. Blundell,et al.  New protein fold revealed by a 2.3-Å resolution crystal structure of nerve growth factor , 1991, Nature.

[36]  S. Smith‐Gill,et al.  Experimental analysis by site-directed mutagenesis of somatic mutation effects on affinity and fine specificity in antibodies specific for lysozyme. , 1992, Journal of immunology.

[37]  R. Huber,et al.  Refined structure of the hirudin-thrombin complex. , 1991, Journal of molecular biology.

[38]  T. Bhat,et al.  Bound water molecules and conformational stabilization help mediate an antigen-antibody association. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[39]  T. N. Bhat,et al.  Small rearrangements in structures of Fv and Fab fragments of antibody D 1.3 on antigen binding , 1990, Nature.

[40]  J Deisenhofer,et al.  Structure of the complex formed by bovine trypsin and bovine pancreatic trypsin inhibitor. II. Crystallographic refinement at 1.9 A resolution. , 1974, Journal of molecular biology.

[41]  B. Tidor,et al.  Do salt bridges stabilize proteins? A continuum electrostatic analysis , 1994, Protein science : a publication of the Protein Society.

[42]  G. Cohen,et al.  Structure of an antibody-antigen complex: crystal structure of the HyHEL-10 Fab-lysozyme complex. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[43]  H Oschkinat,et al.  Receptor binding properties of four‐helix‐bundle growth factors deduced from electrostatic analysis , 1994, Protein science : a publication of the Protein Society.

[44]  C. Chothia,et al.  The structure of protein-protein recognition sites. , 1990, The Journal of biological chemistry.

[45]  M. L. Connolly.  Analytical molecular surface calculation , 1983 .

[46]  M. Karplus,et al.  CHARMM: A program for macromolecular energy, minimization, and dynamics calculations , 1983 .

[47]  J. Thornton,et al.  Ion-pairs in proteins. , 1983, Journal of molecular biology.

[48]  M J Sternberg,et al.  A continuum model for protein-protein interactions: application to the docking problem. , 1995, Journal of molecular biology.

[49]  A J Olson,et al.  Electrostatic orientation of the electron-transfer complex between plastocyanin and cytochrome c. , 1991, The Journal of biological chemistry.

[50]  E. Baker,et al.  Hydrogen bonding in globular proteins. , 1984, Progress in biophysics and molecular biology.

[51]  J Novotny,et al.  Electrostatic fields in antibodies and antibody/antigen complexes. , 1992, Progress in biophysics and molecular biology.

[52]  W G Laver,et al.  The structure of a complex between the NC10 antibody and influenza virus neuraminidase and comparison with the overlapping binding site of the NC41 antibody. , 1994, Structure.

[53]  S. Subramaniam,et al.  Role of electrostatics in antibody-antigen association: anti-hen egg lysozyme/lysozyme complex (HyHEL-5/HEL). , 1994, Journal of biomolecular structure & dynamics.