5jae

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LeuT in the outward-oriented, Na+-free return state, P21 form at pH 6.5

Structural highlights

5jae is a 2 chain structure with sequence from Aquifex aeolicus VF5. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.5Å
Ligands:BOG
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

O67854_AQUAE

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.

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References

  1. 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

Contents


PDB ID 5jae

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