Biochemistry, Molecular Biology
Indiana University
One of the main objectives of the research performed in the Cochran laboratory is to study and understand the details of mechanochemical force transduction in kinesin superfamily motor proteins and elucidate how microtubules stimulate their ATPase activity. To achieve this goal, we will study the detailed structure and thermodynamic energy landscape of an unconventional kinesin, kinesin-10/NOD to determine differences between motile and non-motile kinesin mechanochemistry. In addition, we will characterize our engineered biochemical “metal switch” for kinesin and myosin ATPases as well as small G proteins using a novel experimental approach to probe functional metal-enzyme interactions. Finally, we will investigate the high resolution structure of a kinesin motor in complex with tubulin in order to visualize the detailed mechanism by which interaction with microtubules accelerates the kinesin ATP hydrolysis cycle. The knowledge acquired from the proposed research will expand our understanding of kinesin-MT and other protein-MT systems and will provide valuable insights into possible avenues for therapeutic targeting to combat diseases such as Alzheimer’s, Parkinson’s, and cancer