Revealing an outward-facing open conformational state in a CLC Cl(-)/H(+) exchange transporter.

ABSTRACT: CLC secondary active transporters exchange Cl(-) for H(+). Crystal structures have suggested that the conformational change from occluded to outward-facing states is unusually simple, involving only the rotation of a conserved glutamate (Gluex) upon its protonation. Using (19)F NMR, we show that as [H(+)] is increased to protonate Gluex and enrich the outward-facing state, a residue ~20 Å away from Gluex, near the subunit interface, moves from buried to solvent-exposed. Consistent with functional relevance of this motion, constriction via inter-subunit cross-linking reduces transport. Molecular dynamics simulations indicate that the cross-link dampens extracellular gate-opening motions. In support of this model, mutations that decrease steric contact between Helix N (part of the extracellu

SUBMITTER: Khantwal CM 

PROVIDER: S-EPMC4769167 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature