Coupled global and local changes direct substrate translocation by neurotransmitter-sodium symporter ortholog LeuT.

ABSTRACT: Significant advances have been made in recent years in characterizing neurotransmitter:sodium symporter (NSS) family structure and function. Yet, many time-resolved events and intermediates that control the various stages of transport cycle remain to be elucidated. Whether NSSs harbor one or two sites for binding their substrates (neurotransmitters or amino acids), and what the role of the secondary site S2 is, if any, are still unresolved. Using molecular modeling and simulations for LeuT, a bacterial NSS, we present a comprehensive account of substrate-binding and -stabilization events, and subsequently triggered interactions leading to substrate (alanine) release. LeuT instantaneous conformation as it reconfigures from substrate-receiving (outward-facing) to -releasing (inward-facing) s

SUBMITTER: Cheng MH 

PROVIDER: S-EPMC3736663 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature