Flexible gates generate occluded intermediates in the transport cycle of LacY.

ABSTRACT: The major facilitator superfamily (MFS) transporter lactose permease (LacY) alternates between cytoplasmic and periplasmic open conformations to co-transport a sugar molecule together with a proton across the plasma membrane. Indirect experimental evidence suggested the existence of an occluded transition intermediate of LacY, which would prevent leaking of the proton gradient. As no experimental structure is known, the conformational transition is not fully understood in atomic detail. We simulated transition events from a cytoplasmic open conformation to a periplasmic open conformation with the dynamic importance sampling molecular dynamics method and observed occluded intermediates. Analysis of water permeation pathways and the electrostatic free-energy landscape of a solvated proton in

SUBMITTER: Stelzl LS 

PROVIDER: S-EPMC3905165 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature