Michael Marty (University of Arizona)


Location: B01 McCourtney Hall (Please Note Room)

Abstract:  Due to their important biochemical roles, membrane proteins are important drug targets. Although lipids can influence membrane protein function, the chemistry of lipid binding remains difficult to study because protein-lipid interactions are polydisperse, competitive, and transient. We have been developing new analytical approaches to quantify protein-lipid interactions in bilayers and understand how membrane proteins remodel their surrounding lipid environment. In one new approach, we are using lipidomic mass spectrometry (MS) to quantify the exchange of lipids between lipoprotein nanodiscs with and without an embedded membrane protein. Shifts in the lipid distribution towards the membrane protein nanodiscs reveal lipid binding, and titrations allow measurement of the optimal lipid composition for the membrane protein. We have also been studying how lipids bind to specific sites on membrane proteins. Here, we mutate different potential lipid binding sites on the membrane protein surface and simultaneously measure binding to the mutant and wild type versions with native MS. By performing these experiments at different temperatures, we uncover the thermodynamics of lipid binding to specific residues and discover the relative affinities of different lipid binding sites. Ultimately, we expect these unique combinations of nanodiscs and MS will provide new insights into how lipids modulate the structure and function of membrane proteins.

Originally published at chemistry.nd.edu.