Alternating access mechanisms of LeuT-fold transporters: trailblazing towards the promised energy landscapes

• Published in: Current opinion in structural biology Vol. 45; pp. 100 - 108
• Main Authors: Kazmier, Kelli, Claxton, Derek P, Mchaourab, Hassane S
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-08-2017
• ISSN: 0959-440X; 1879-033X
• DOI: 10.1016/j.sbi.2016.12.006

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•Alternating access in the LeuT-fold class of transporters is discussed.•Structural analysis suggests mechanistic divergence among class members.•Ligand-dependent conformational equilibria is a defining feature of transport.•Descriptions of transport energy landscapes require a multifaceted approach.
Secondary active transporters couple the uphill translocation of substrates to electrochemical ion gradients. Transporter conformational motion, generically referred to as alternating access, enables a central ligand binding site to change its orientation relative to the membrane. Here we review themes of alternating access and the transduction of ion gradient energy to power this process in the LeuT-fold class of transporters where crystallographic, computational and spectroscopic approaches have converged to yield detailed models of transport cycles. Specifically, we compare findings for the Na+-coupled amino acid transporter LeuT and the Na+-coupled hydantoin transporter Mhp1. Although these studies have illuminated multiple aspects of transporter structures and dynamics, a number of questions remain unresolved that so far hinder understanding transport mechanisms in an energy landscape perspective.