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Structural modeling of the complex between an acetylcholine receptor‐mimicking antibody and its snake toxin antigen
Author(s) -
TenetteSouaille Catherine,
Smith Jeremy C.
Publication year - 1998
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/(sici)1097-0134(19980215)30:3<249::aid-prot5>3.0.co;2-f
Subject(s) - epitope , complementarity determining region , single domain antibody , chemistry , epitope mapping , acetylcholine receptor , mutagenesis , binding site , protein structure , antigen , antibody , toxin , biophysics , molecular model , computational biology , receptor , stereochemistry , monoclonal antibody , biology , biochemistry , immunology , mutation , gene
The antibody Mα2‐3 neutralizes the functional, acetylcholine receptor binding activity of its antigen, neurotoxin α, and exhibits several other properties in common with the receptor itself. We present here the results of calculations examining the three‐dimensional structure of the toxin α:Mα2‐3 complex. The antigen structure, determined by nuclear magnetic resonance spectroscopy, 1 was docked to models of the variable fragment of the antibody combining site 2 by using a method based on surface complementarity and maximization of buried surface area 3,4 while taking into account the possibility of conformational change on complexation. Extensive experimental information on the location of the functional epitope was incorporated into the analysis and used to screen candidate geometries of the complex resulting from the modeling. Eight plausible structures that are in accord with the experimental data were derived. Common structural features of the models are discussed, and residues of the antibody‐combining site that are expected to play important roles in complexation are identified. In particular, three epitope residues that, according to mutagenesis experiments, make particularly strong contributions to the binding, interact excentrically and do not make contact with the central loops of the combining site, L3 and H3. Proteins 30:249–263, 1998. © 1998 Wiley‐Liss, Inc.