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Molecular modeling of c‐erbB2 receptor dimerization: Coiled‐coil structure of wild and oncogenic transmembrane domains—Stabilization by interhelical hydrogen bonds in the oncogenic form
Author(s) -
Garnier Norbert,
Genest Daniel,
Duneau Jean Pierre,
Genest Monique
Publication year - 1997
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/(sici)1097-0282(199708)42:2<157::aid-bip5>3.0.co;2-m
Subject(s) - chemistry , transmembrane domain , hydrogen bond , transmembrane protein , coiled coil , molecular dynamics , helix (gastropod) , mutant , stereochemistry , molecular model , crystallography , point mutation , side chain , biophysics , molecule , membrane , receptor , biochemistry , computational chemistry , gene , ecology , organic chemistry , snail , biology , polymer
Abstract Dimerization models of c‐erbB2 transmembrane domains (Leu651‐Ile675) are studied by molecular mechanics and molecular dynamics simulations. Both wild and Glu mutated transmembrane helices exhibit the same relative orientation for favorable associations and dimerize preferentially in left‐handed coiled‐coil structures. The mutation point 659 belongs to the interfacing residues, and in the transforming domain, symmetric hydrogen bonds between Glu carboxylic groups stabilize the dimeric structure. The same helix packing found for the wild dimers, except side‐chain—side‐chain hydrogen bonds, suggests that the transmembrane domains dimerize according to similar process. Structural and energetical characterization of the models are presented. © 1997 John Wiley & Sons, Inc. Biopoly 42: 157–168, 1997