"Probing Molecular War at the Cell-Membrane Interface"
Membrane proteins are an exciting class of biomacromolecules and play important roles in a variety of biological processes that are directly linked to major diseases including cancer, aging-related diseases, and infectious diseases. A complete understanding of their function can only be accomplished using high-resolution structures and dynamics. In spite of recent developments in structural biology, membrane proteins continue to pose tremendous challenges to most biophysical techniques. A major area of research in my group is focused on the development of NMR techniques to study the dynamic structures of membrane bound proteins such as cytochrome b5, cytochrome P450 and cytochrome P450-reductase. In my talk, I will present strategies to study the structure and dynamics of these challenging systems and also on the electron transfer mechanism that enables the enzymatic function of P450. In the second-half of my talk, atomic-level resolution NMR structures of amyloidogenic proteins revealing the misfolding pathway and early intermediates that play key roles in amyloid toxicity will be presented. Specifically, the various roles of lipid membrane, metals, and amyloid inhibitors will be discussed.
References:
J. Biol. Chem. (2015) 290:12705-18; 290: 4843-55; 288:22080-95.
Chem. Soc. Rev. (2014) 43:6692-6700; J. Phys. Chem. Lett. (2014) 5:1864.