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

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