Membrane transporter dimerization driven by differential lipid solvation energetics of dissociated and associated states.

ABSTRACT: Over two-thirds of integral membrane proteins of known structure assemble into oligomers. Yet, the forces that drive the association of these proteins remain to be delineated, as the lipid bilayer is a solvent environment that is both structurally and chemically complex. In this study, we reveal how the lipid solvent defines the dimerization equilibrium of the CLC-ec1 Cl^-/H⁺ antiporter. Integrating experimental and computational approaches, we show that monomers associate to avoid a thinned-membrane defect formed by hydrophobic mismatch at their exposed dimerization interfaces. In this defect, lipids are strongly tilted and less densely packed than in the bulk, with a larger degree of entanglement between opposing leaflets and greater water penetration into the bilaye

SUBMITTER: Chadda R 

PROVIDER: S-EPMC8116059 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature