Gordeliy Team

Principal investigator: Valentin Gordeliy, Research Director CEA

Research topics

The goal of our team is a deep integration of two, usually disconnected, parts: the elucidation of high resolution structures and molecular mechanisms of function of membrane proteins as well as the development of efficient approaches to membrane protein crystallization. Systematic structural characterization of in-meso systems in the course of crystallization will accompany crystallization experiments with all the proteins under discussion. Development of the methods of crystallization will contribute to the platform which is installed at IBS to make a principal step toward high throughput crystallography of membrane proteins by reducing the volume of a crystallization probe from about 1 μl to 10 nl.

The project’s strategy is to further develop the in meso crystallization approach. Recent breakthroughs, including a very recent one – the crystallization of human beta2-adrenergic G-protein coupled receptor, achieved by using the in meso method showed its high potential. However, crystallization of membrane proteins is still a challenge. Our recent work on the NpSRII+NpHtrII complex (Nature, 2002 and Nature, 2006) as well as bacteriorhodopsin (BR) required considerable deviations from the existing in meso crystallization protocols and showed that there are more efficient membrane-like systems for membrane protein crystallization. These studies also demonstrated that one of the main barriers on the way to more efficient methods is a huge gap in our knowledge of the systems used for membrane protein crystallization. Therefore, a key element of our projects will be structural characterization of in meso systems in the course of membrane protein crystallization.

Structure and mechanism of function of retinal proteins are under the intense investigations in our team. Our plan is to obtain highest resolution structures of the proteins to elucidate key elements of their molecular mechanisms of action. In course of study of molecular mechanisms of intercellular communications the goal is to obtain high resolution structures of gap junctions in open and closed states formed by human connexins. In addition we are planning to participate in in vivo and in vitro studies of the role of the gap junctions in cell differentiations and tumor promotion.