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.
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.
Garnier
N
N
Centre de Biophysique Moléculaire, CNRS, Université d'Orleans, France.
Genest
D
D
Duneau
J P
JP
Genest
M
M
D000595:Amino Acid Sequence; D003198:Computer Simulation; D019281:Dimerization; D018698:Glutamic Acid; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010446:Peptide Fragments / Q000737:chemistry; D017433:Protein Structure, Secondary; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000737:chemistry*; D011994:Recombinant Proteins / Q000737:chemistry
D018698:Glutamic Acid; D010446:Peptide Fragments; D018719:Erb-b2 Receptor Tyrosine Kinases; D011994:Recombinant Proteins