Structural highlights
Publication Abstract from PubMed
Bacterial members of the neurotransmitter:sodium symporter (NSS) family perform Na(+)-dependent amino-acid uptake and extrude H(+) in return. Previous NSS structures represent intermediates of Na(+)/substrate binding or intracellular release, but not the inward-to-outward return transition. Here we report crystal structures of Aquifex aeolicus LeuT in an outward-oriented, Na(+)- and substrate-free state likely to be H(+)-occluded. We find a remarkable rotation of the conserved Leu25 into the empty substrate-binding pocket and rearrangements of the empty Na(+) sites. Mutational studies of the equivalent Leu99 in the human serotonin transporter show a critical role of this residue on the transport rate. Molecular dynamics simulations show that extracellular Na(+) is blocked unless Leu25 is rotated out of the substrate-binding pocket. We propose that Leu25 facilitates the inward-to-outward transition by compensating a Na(+)- and substrate-free state and acts as the gatekeeper for Na(+) binding that prevents leak in inward-outward return transitions.
A conserved leucine occupies the empty substrate site of LeuT in the Na(+)-free return state.,Malinauskaite L, Said S, Sahin C, Grouleff J, Shahsavar A, Bjerregaard H, Noer P, Severinsen K, Boesen T, Schiott B, Sinning S, Nissen P Nat Commun. 2016 May 25;7:11673. doi: 10.1038/ncomms11673. PMID:27221344[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Malinauskaite L, Said S, Sahin C, Grouleff J, Shahsavar A, Bjerregaard H, Noer P, Severinsen K, Boesen T, Schiott B, Sinning S, Nissen P. A conserved leucine occupies the empty substrate site of LeuT in the Na(+)-free return state. Nat Commun. 2016 May 25;7:11673. doi: 10.1038/ncomms11673. PMID:27221344 doi:http://dx.doi.org/10.1038/ncomms11673
