Accession Number : ADA314092

Title :   Rotational Resonance NMR Structural Studies of the new Receptor Transmembrane Domain.

Descriptive Note : Final rept. 23 May 94-23 Jun 96,

Corporate Author : YALE UNIV NEW HAVEN CT

Personal Author(s) : Smith, Steven O.

PDF Url : ADA314092

Report Date : JUL 1996

Pagination or Media Count : 38

Abstract : The objective of this Exploratory Award was to establish whether magic angle spinning NMR and polarized infrared Spectroscopy could be applied to obtain high resolution structural constraints on the transmembrane domain of the neu/erbB-2 receptor in membrane environments. Such data would be able to address specific models for receptor activation by the transforming glutamic acid 664 mutation. The ultimate goal has been to obtain a high resolution 3D structure of the transmembrane domain of the constitutively activated receptor that can be used to establish the activation mechanism and possibly serve as a guide to the design of competitive inhibitors. The results obtained to date demonstrate that the approach outlined was successful and has provided the ground work for further studies. The major conclusion that can be drawn thus far is that the valine to glutamic acid mutation that activates the neu receptor, and is associated with a large number of breast cancers, functions by stabilizing receptor dimers via strong head-to-head hydrogen bonding interactions of the protonated glutamic acid COOH side chain.

Descriptors :   *NUCLEAR MAGNETIC RESONANCE, *MEMBRANES, STABILIZATION, ANGLES, POLARIZATION, ACTIVATION, INFRARED SPECTROSCOPY, COMPETITION, ENVIRONMENTS, MODELS, STRUCTURAL PROPERTIES, GLUTAMIC ACID, HIGH RESOLUTION, MUTATIONS, CHEMICAL BONDS, RESONANCE, SPINNING(MOTION), INHIBITORS, ROTATION, SENSE ORGANS, AMINO ACIDS, DIMERS, BREAST CANCER.

Subject Categories : Biology
      Atomic and Molecular Physics and Spectroscopy

Distribution Statement : APPROVED FOR PUBLIC RELEASE