Spatial structure of the dimeric transmembrane domain of the growth factor receptor ErbB2 presumably corresponding to the receptor active state

J Biol Chem. 2008 Mar 14;283(11):6950-6. doi: 10.1074/jbc.M709202200. Epub 2008 Jan 4.

Abstract

Proper lateral dimerization of the transmembrane domains of receptor tyrosine kinases is required for biochemical signal transduction across the plasma membrane. The spatial structure of the dimeric transmembrane domain of the growth factor receptor ErbB2 embedded into lipid bicelles was obtained by solution NMR, followed by molecular dynamics relaxation in an explicit lipid bilayer. ErbB2 transmembrane segments associate in a right-handed alpha-helical bundle through the N-terminal tandem GG4-like motif Thr652-X3-Ser656-X3-Gly660, providing an explanation for the pathogenic power of some oncogenic mutations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Cell Membrane / metabolism*
  • Dimerization
  • Humans
  • Lipid Bilayers / chemistry
  • Lipids / chemistry
  • Magnetic Resonance Spectroscopy / methods
  • Molecular Conformation
  • Mutation
  • Protein Conformation
  • Protein Folding
  • Protein Structure, Tertiary
  • Receptor Protein-Tyrosine Kinases / chemistry
  • Receptor, ErbB-2 / chemistry*

Substances

  • Lipid Bilayers
  • Lipids
  • ERBB2 protein, human
  • Receptor Protein-Tyrosine Kinases
  • Receptor, ErbB-2

Associated data

  • PDB/2JWA