PATHWAYS OF CONFORMATIONAL TRANSITIONS CRUCIAL FOR SIGNALING, ENZYME CATALYSIS

Carnegie-Mellon University, Pittsburgh PA

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We propose a detailed investigation of the mechanism of conformational transition for three diverse proteins representing a signaling protein, an enzyme and a regulator through protein/protein interaction. Recent experiments conducted within our group on these three systems have shown that their ability of interconverting between different coexisting conformers is key to the accomplishment of their biological function. The goal of our investigations is to quantitatively model these conformational changes, and to understand at a molecular level the specific interactions most relevant in triggering and accompanying the interconversions. The proposed work is funded by the Dept of Energy (Award No. DE-FG02-05ER15699) and the Howard Hughes Medical Institute.