Ion/substrate-dependent conformational dynamics of a bacterial homolog of neurotransmitter:sodium symporters.

ABSTRACT: Crystallographic, computational and functional analyses of LeuT have revealed details of the molecular architecture of Na(+)-coupled transporters and the mechanistic nature of ion/substrate coupling, but the conformational changes that support a functional transport cycle have yet to be described fully. We have used site-directed spin labeling and electron paramagnetic resonance (EPR) analysis to capture the dynamics of LeuT in the region of the extracellular vestibule associated with the binding of Na(+) and leucine. The results outline the Na(+)-dependent formation of a dynamic outward-facing intermediate that exposes the primary substrate binding site and the conformational changes that occlude this binding site upon subsequent binding of the leucine substrate. Furthermore, the binding

SUBMITTER: Claxton DP 

PROVIDER: S-EPMC3245867 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature