Lynmarie K. Thompson
Professor of Chemistry, University of Massachusetts
Director, Chemistry Biology Interface Training Program
Ph.D.: Yale University
Postdoctoral Training: Massachusetts Institute of Technology
Membrane proteins are key players in the essential cellular processes of energy and signal transduction. Our laboratory is interested in understanding the molecular mechanisms of such processes: for instance, how is a signal transmitted across a membrane?
The transmembrane receptors of bacterial chemotaxis bind specific attractant molecules and transmit this information across the membrane to direct the swimming of the bacterium. Ligand binding to this receptor is thought to cause a conformational change that propagates the signal across the membrane. However, as with most membrane proteins, the traditional tools of structural biology have not been able to provide structures of the intact receptor to follow this conformational change. We are using recently developed solid-state NMR methods to measure selected distances in membrane-bound proteins, providing structural information that can map a ligand binding site or test a proposed mechanism.
We have used a powerful site-directed distance measurement strategy to measure helix-helix distances in the periplasmic domain of the intact serine receptor which are consistent in magnitude with a proposed ligand-induced piston mechanism. Additional distance measurements are in progress to map the type of structural change: does ligand-binding induce translation, rotation, or pivoting motions of the helices? By measuring the effect of ligand-binding on helix-helix distances throughout the receptor, these studies are providing a molecular picture of how a protein transmits a signal across a membrane.
Our overall strategy is to combine site-directed NMR distance measurements with other biophysical approaches to probe the structure and mechanism of membrane proteins. Membrane proteins are both tremendously important (as pharmaceutical targets for example) and poorly understood, making this an area rich in opportunities for exciting research.