Biophysical Society Conference | Tahoe 2024

Molecular Biophysics of Membranes

Tuesday Speaker Abstracts

BEYOND BAR DOMAINS: UNDERSTANDING MEMBRANE REMODELING THROUGH MOLECULAR SIMULATION Jeriann Beiter 1 ; Shan-Shan Lin 3 ; Aurelie Bertin 2 ; John Manzi 2 ; Senthil Arumugam 4 ; Ya Wen Liu 3 ; Feng-Ching Tsai 2 ; Patricia Bassereau 2 ; Gregory A Voth 1 ; 1 University of Chicago, Chemistry, Chicago, IL, USA 2 Institut Curie, UMR 168, Paris, France 3 National Taiwan University College of Medicine, Institute of Molecular Medicine, Taipei, Taiwan 4 Monash University, Anatomy and Developmental Biology, Melbourne, Australia Bin/Amphiphysin/Rvs (BAR) domains are one of the most closely studied peripheral proteins, and are involved in seemingly all cellular membrane remodeling events, particularly at the plasma membrane. Both in vitro and in vivo work have demonstrated the dramatic tubulation activity of BAR domains alone and in concert with other peripheral proteins, and the general dependence of this effect on the presence of negatively charged lipids such as phosphatidylserine (PS) and phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2). Using atomistic and coarse-grained (CG) molecular dynamics simulation in tandem with in vitro and in vivo imaging, we investigate at the molecular level the interactions of BAR domains with other protein domains and with the underlying lipids in the membrane. To demonstrate the general principles we have learned in our work, we study two example BAR domain systems: the paradigmatic endophilin and the PX BAR domain of sorting nexin 9 (SNX9). We find that BAR domains interact synergistically with other domains within the same protein, but the collective remodeling behavior of these proteins are not mediated by direct protein/protein interactions. Rather, local non-stoichiometric protein/lipid interactions act to generate long-range clustering, particularly through modulating the lipid diffusivity. The implications of this work extend broadly from considerations in structural biology of peripheral membrane proteins to understanding regulation of plasma membrane tension and cell motility.


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