“Driving Forces of Greasy Protein Association in Greasy Membranes”
Host: Jon Silva (WashU Biomedical Engineering (BME))
Abstract: Membrane proteins are the molecular gatekeepers of biology. They govern the passage of charged and polar species in and out of cells, thus enabling the storage of potential energy that fuels life. Despite their overwhelming importance, we still do not understand the basic physical reasons why membrane proteins associate and assemble to form stable structures in the lipid bilayer. For soluble proteins, the burial of hydrophobic groups away from aqueous interfaces is a major driving force, but membrane-embedded proteins cannot experience hydrophobic forces, as the lipid bilayer lacks water. A fundamental conundrum thus arises: how does a greasy protein surface find its greasy protein partner in the greasy lipid bilayer to fold faithfully into its native structure? In our lab, we measure the thermodynamics of membrane protein assembly, directly in lipid bilayers, using model systems of membrane protein dimerization. We approach these three curious questions with a variety of experimental techniques including membrane protein purification and functional reconstitution, electrophysiology, x-ray crystallography, single -molecule TIRF microscopy and computational modeling. With this, we are able to fully interrogate the physical driving forces that determine how and why greasy membrane proteins form stable structures inside the greasy lipid membrane.
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