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

Nature Structural Biology volume 3, pages 252–258 (1996)Cite this article

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 α-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.

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Authors and Affiliations

  1. Department of Molecular Biophysics and Biochemistry, Yale University, 266 Whitney Avenue, Box 208114, New Haven, Connecticut, 06520-8114, USA

    Steven O. Smith & Charles S. Smith

  2. Boehringer-Ingelheim, Ridgefield, Connecticut, 06877, USA

    Barbara J. Bormann

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  2. Charles S. Smith
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  3. Barbara J. Bormann
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Smith, S., Smith, C. & Bormann, B. Strong hydrogen bonding interactions involving a buried glutamic acid in the transmembrane sequence of the neu/erbB-2 receptor. Nat Struct Mol Biol 3, 252–258 (1996). https://doi.org/10.1038/nsb0396-252

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