Rotational Resonance NMR Structural Studies of the Neu Receptor Transmembrane Domain.
Annual rept. 23 May 94-23 May 95,
YALE UNIV NEW HAVEN CT
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In order to determine the structure of the transmembrane domain of the neuerbB-2 receptor and address the molecular mechanism of receptor activation by the transforming V664 to E664 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 E664 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 E664 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 DMPCDMPS membranes argues that the V664 to E664 mutation causes the transmembrane domain to dimerize.
- Atomic and Molecular Physics and Spectroscopy