Strong hydrogen bonding interactions involving a buried glutamic acid in the transmembrane sequence of the neu/erbB-2 receptor

Nat Struct Biol. 1996 Mar;3(3):252-8. doi: 10.1038/nsb0396-252.

Abstract

The receptor tyrosine kinase encoded by the neu/erbB-2 proto-oncogene is constitutively activated by a single valine to glutamic acid substitution at position 664 in the predicted membrane-spanning sequence of the receptor. We have explored the structural changes involved in receptor activation with polarized FTIR and magic angle spinning NMR spectroscopy. The hydrophobic transmembrane sequence folds into a well-defined alpha-helical structure spanning the membrane bilayer. Measurements of the pKa and 13C chemical shift anisotropy of Glu 664 reveal that the side chain carboxyl group is protonated and strongly hydrogen bonded. These studies provide direct evidence for glutamate hydrogen-bonding interactions in the mechanism of receptor dimerization and activation.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Fluorescence Polarization
  • Glutamic Acid*
  • Hydrogen Bonding
  • Kinetics
  • Lipid Bilayers
  • Models, Structural
  • Molecular Sequence Data
  • Peptide Fragments / chemical synthesis
  • Peptide Fragments / chemistry
  • Peptide Fragments / isolation & purification
  • Protein Structure, Secondary*
  • Rats
  • Receptor Protein-Tyrosine Kinases / chemistry*
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Receptor, ErbB-2 / chemistry*
  • Receptor, ErbB-2 / metabolism*
  • Spectroscopy, Fourier Transform Infrared

Substances

  • Lipid Bilayers
  • Peptide Fragments
  • Glutamic Acid
  • Receptor Protein-Tyrosine Kinases
  • Receptor, ErbB-2