Biophysical Society Conference | Tahoe 2024

Molecular Biophysics of Membranes

Wednesday Speaker Abstracts

A MOLECULAR MODEL FOR ION CHANNEL AND TRANSPORTER DIMERIZATION IN MEMBRANES Janice L. Robertson ; 1 Washington University School of Medicine in St. Louis, Biochemistry and Molecular Biophysics, St. Louis, MO, USA Ion channels and transporters are the molecular gatekeepers of biology, governing the passage of atoms and molecules in and out of cells. They provide essential nutrients for metabolism, eliminate waste, enable cell-to-cell communication, and store the potential energy that fuels life. Yet, despite their overwhelming importance, we lack a physical and molecular understanding of why membrane transport proteins form stable structures that enable their specific functions within the oil-filled environment of the lipid bilayer. Our lack of understanding here is well rationalized by the inherent challenge of measuring equilibrium reactions of membrane protein assembly in membranes, compounded by the complexity of the reaction solvent as a structured lipid bilayer. However, through a combination of novel experimental single-molecule microscopy approaches coupled with coarse-grained and all-atom computational modeling, we can now measure equilibrium constants of protein association in membranes and dissect out the important molecular contributions from the protein and surrounding membrane. Here, I present our results on two systems where reversible binding within membranes can be quantitatively assessed - the homodimeric CLC-ec1 chloride/proton antiporter and the dual-topology homodimeric Fluc fluoride ion channel. By combining experimental and computational studies, we identify a driving force for protein association that arises from state-dependent perturbation of the membrane structure, and a mechanism for tuning dimerization stability by altering solvation energetics through preferential solvation. These results present a generalizable driving force for membrane protein assembly in membranes that is expected to apply to all ion channels and transporters.

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