Research Topics

STRUCTURAL & ENERGETIC PRINCIPLES OF MEMBRANE PROTEINS

Summary

Principal Investigator: KAREN FLEMING
Abstract: DESCRIPTION (Adapted from abstract): Understanding of structural energetics of membrane proteins lags far behind that of soluble proteins. In part, this is due to the rarity of membrane protein structures known at atomic resolution. Equally responsible, however, is the lack of quantitative thermodynamic information on membrane protein folding and assembly. The work being proposed will provide data concerning the specificity and stability of helix-helix associations in membrane proteins. The experimental approach will produce a detailed structural and thermodynamic analysis of the glycophorin transmembrane domain dimer. Novel thermodynamic measurements using ultracentrifugation will permit a quantitative assessment of the sequence dependence of dimer stability through numerous site specific mutants. Structure determination by solution NMR in detergent micelles of the same mutants will provide a structural framework on which to understand the experimentally observed effects on the monomer dimer equilibrium. Principles that emerge from the integration of the structural and thermodynamic measurements will be incorporated into existing computational algorithms to improve their performance in modeling, prediction, and design efforts for membrane proteins.
Funding Period: 1999-08-01 - 2004-07-31
more information: NIH RePORT