High-pH structure of EmrE reveals the mechanism of proton-coupled substrate transport.

ABSTRACT: The homo-dimeric bacterial membrane protein EmrE effluxes polyaromatic cationic substrates in a proton-coupled manner to cause multidrug resistance. We recently determined the structure of substrate-bound EmrE in phospholipid bilayers by measuring hundreds of protein-ligand H^N-F distances for a fluorinated substrate, 4-fluoro-tetraphenylphosphonium (F₄-TPP⁺), using solid-state NMR. This structure was solved at low pH where one of the two proton-binding Glu14 residues is protonated. Here, to understand how substrate transport depends on pH, we determine the structure of the EmrE-TPP complex at high pH, where both Glu14 residues are deprotonated. The high-pH complex exhibits an elongated and hydrated binding pocket in which the substrate is similarly exposed

SUBMITTER: Shcherbakov AA 

PROVIDER: S-EPMC8857205 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature