Accession Number : ADA295872
Title : Rotational Resonance NMR Structural Studies of the Neu Receptor Transmembrane Domain.
Descriptive Note : Annual rept. 23 May 94-23 May 95,
Corporate Author : YALE UNIV NEW HAVEN CT
Personal Author(s) : Smith, Steven O.
PDF Url : ADA295872
Report Date : 23 MAY 1995
Pagination or Media Count : 13
Abstract : In order to determine the structure of the transmembrane domain of the neu/erbB-2 receptor and address the molecular mechanism of receptor activation by the transforming V664 to E(664) mutation, magic angle spinning NMR and polarized Fourier transform infrared studies have been undertaken. These studies show that the region C-terminal to position 664 is helical and oriented roughly perpendicular to the membrane plane. When the E(664) carboxyl group is deprotonated, the region N-terminal to position 664 unfolds and the COO-group is exposed to the polar membrane interface. Protonation allows the peptide to adopt a helical conformation oriented perpendicular to the membrane plane. The pKa of the E(664) side chain is shifted by the membrane surface charge. Under conditions approximating those in native membranes, the carboxyl group readily partitions into the membrane. The high pKa observed for the E664 carboxyl group and increased orientation in DMPC:DMPS membranes argues that the V664 to E664 mutation causes the transmembrane domain to dimerize.
Descriptors : *NUCLEAR MAGNETIC RESONANCE, *MEMBRANES, ANGLES, POLAR REGIONS, INTERFACES, MOLECULES, STRUCTURAL PROPERTIES, PEPTIDES, SPINNING(MOTION), ROTATION, SENSE ORGANS, HELIXES, STATIC ELECTRICITY, CONFORMITY, CARBOXYL RADICALS.
Subject Categories : Atomic and Molecular Physics and Spectroscopy
Distribution Statement : APPROVED FOR PUBLIC RELEASE