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

By Kelli N Kazmier, D. P. Claxton, Hassane S. Mchaourab. 2016

65 citations recorded by the source corpus.

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.

Subfields: Biophysics, Molecular Biology, Spectroscopy

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Biophysics

1. Diego del Alamo
2. Jens Meiler
3. Davide Sala
4. Hassane S. Mchaourab

In Molecular Biology

1. Diego del Alamo
2. Jens Meiler
3. Davide Sala
4. Hassane S. Mchaourab
5. Björn Wallner
6. David Baker

In Spectroscopy

1. Jens Meiler
2. Davide Sala
3. Diego del Alamo
4. Hassane S. Mchaourab

Citations in the corpus

• Sampling alternative conformational states of transporters and receptors with AlphaFold2 (2022, background): “For example, the vectorial translocation of substrates by transporters is mediated by movements that open and close extra-and intracellular gates ( Drew and Boudker, 2016 ; Kazmier et al., 2017 ).”