Dr. Michael Marty - Revealing membrane interactions with mass spectrometry and nanodiscs - IPBS-Toulouse, Seminar Room

Michael Marty

Department of Chemistry and Biochemistry and Bio5 Institute, University of Arizona, Tucson, AZ

Revealing membrane interactions with mass spectrometry and nanodiscs

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 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 affect oligomerization of membrane proteins into functional complexes using native MS of intact nanodisc complexes. Our goal is to understand how the lipid environment affects oligomerization and drug binding to viral ion channels. 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.

Selected references

• Townsend, J.A.; Sanders, H.M.; Rolland, A.D.; Park, C.K.; Horton, N.C.; Prell, J.S.; Wang, J; Marty, M.T. “Influenza A M2 Channel Oligomerization is Sensitive to its Chemical Environment.” Anal. Chem. 2021, 93, 16273-16281
• Keener, J.E.; Zhang, G.; Marty, M.T. “Native Mass Spectrometry of Membrane Proteins” Anal. Chem. 2020. 93, 583-597.
• Marty, M.T. “Nanodiscs and Mass Spectrometry: Making Membranes Fly” Int. J. Mass Spectrom. 2020, 458, 116436
• Zhang, G.; Keener, J.E.; Marty, M.T. “Measuring Remodeling of the Lipid Environment Surrounding Membrane Proteins with Lipid Exchange and Native Mass Spectrometry.” Anal. Chem. 2020, 92, 5666-5669