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

被引：119

作者：

Smith, SO ^{[1
]}

Smith, CS ^{[1
]}

Bormann, BJ ^{[1
]}

机构：

[1] BOEHRINGER INGELHEIM PHARMACEUT INC,RIDGEFIELD,CT 06877

来源：

NATURE STRUCTURAL BIOLOGY | 1996年 / 3卷 / 03期

关键词：

D O I：

10.1038/nsb0396-252

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 pK(a) and C-13 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.

引用

页码：252 / 258

页数：7

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