Rotational Resonance NMR Structural Studies of the Neu Receptor Transmembrane Domain.
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.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 23, 1995
- Accession Number
- ADA295872
Entities
People
- Steven O. Smith
Organizations
- Yale University