The effect of hydrophilic substitutions and anionic lipids upon the transverse positioning of the transmembrane helix of the ErbB2 (neu) protein incorporated into model membrane vesicles.

Journal of Molecular Biology
Khurshida ShahidullahErwin London

Abstract

The sequence of the transmembrane (TM) helix of ErbB2, a member of the epidermal growth factor receptor (ErbB) family, can influence its activity. In this report, the sequence and lipid dependence of the transverse position of a model-membrane-inserted peptides containing the ErbB2 TM helix and some of the juxtamembrane (JM) residues were studied. For the ErbB2 TM helix inserted into phosphatidylcholine vesicles, the activating V664E mutation was found to induce a transverse shift involving the movement of the E residue toward the membrane surface. This shortened the effective length of the TM-spanning portion of the sequence. The transverse shift was observed with the E664 residue in both the uncharged and charged states, but the extent of the shift was larger when the E residue was charged. When a series of hydrophilic residues was substituted for V664, the resulting transverse shifts at pH 7.0 decreased in the order D,H>E>Q>K>G>V. Except for His, this order is strongly correlated to that reported for the degree to which these substitutions induce cellular transformation when introduced into full-length ErbB2. To examine the effect of lipid on transverse shift, we studied the uncharged V664Q mutation. The presence of 20% of t...Continue Reading

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Citations

Sep 14, 2011·Biochimica Et Biophysica Acta·Edwin LiKalina Hristova
Jul 15, 2016·Biophysical Journal·Angelica SandovalRainer A Böckmann
Sep 22, 2016·Langmuir : the ACS Journal of Surfaces and Colloids·Jamie LeBarron, Erwin London
Oct 11, 2016·Journal of Molecular Biology·Andrew K LewisJonathan N Sachs
Oct 8, 2013·Physical Chemistry Chemical Physics : PCCP·Xavier PrasannaDurba Sengupta
Jan 9, 2014·The Journal of Biological Chemistry·Qingqing Lin, Erwin London
Jun 23, 2021·Proceedings of the National Academy of Sciences of the United States of America·Lam-Kiu FongWilliam F DeGrado
Aug 15, 2012·Journal of the American Chemical Society·Anton A PolyanskyRoman G Efremov
May 11, 2019·Biochimica Et Biophysica Acta. Biomembranes·Morgan A HitchnerGregory A Caputo

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