Detailed description of an alpha helix-->pi bulge transition detected by molecular dynamics simulations of the p185c-erbB2 V659G transmembrane domain.
Molecular dynamics simulations of a 29-residue peptide including the transmembrane domain of the V659G mutant of the c-erbB2 protein demonstrate important dynamical behavior. Although the alpha helix is the structure commonly assumed for transmembrane hydrophobic segments, we found that hydrogen bond rearrangements can occur, giving rise to a structural deformation termed pi bulge stabilized by successive hydrogen bonds of pi helix type. A series of simulations enables us to give a detailed description, at the atomic level, of the alpha helix->pi bulge transition. The major consequence of this deformation covering one and a half turn of helix results in a noticeable shift around the helix axis of the C-Terminal residues relatively to those of the N-terminus. Such a deformation closely related to structural motifs described in the literature, induces a change in the distribution of the residues along the helix faces which could modulate the protein activity mediated by a dimerization process.
Duneau
J P
JP
Centre de Biophysique Moléculaire, Orléans, France. duneau@cnrs-orleans.fr
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D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000737:chemistry; D003198:Computer Simulation; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D010455:Peptides / Q000737:chemistry; D017433:Protein Structure, Secondary; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000737:chemistry*
D010455:Peptides; D018719:Erb-b2 Receptor Tyrosine Kinases