ArticleNature communications2016
A conserved leucine occupies the empty substrate site of LeuT in the Na(+)-free return state.
Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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39 citing papers in PubMed, 73 citations in OpenAlex.
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- A reversible allosteric inhibitor of GlyT2 alleviates neuropathic pain without on-target side effects.bioRxiv : the preprint server for biology · 2025Article
- Exploring the Structural Dynamics of LeuT Using EPR Spectroscopy: A Focus on Transmembrane Helix 10.Journal of neurochemistry · 2025Article
- Monitoring conformational changes in the human neurotransmitter transporter homologue LeuT withJournal of neurochemistry · 2025Article
- Identification of the potassium-binding site in serotonin transporter.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Conformational free-energy landscapes of a NaProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Exploring the KeLife · 2024Article
- Slc20a1 and Slc20a2 regulate neuronal plasticity and cognition independently of their phosphate transport ability.Cell death & disease · 2024Article
- Conservation of knotted and slipknotted topology in transmembrane transporters.Biophysical journal · 2023Article
- Taurine and Creatine Transporters as Potential Drug Targets in Cancer Therapy.International journal of molecular sciences · 2023Review
- Effects of the N-terminal dynamics on the conformational states of human dopamine transporter.Biophysical chemistry · 2022Article
- General principles of secondary active transporter function.Biophysics reviews · 2022Review
- The Lepidopteran KAAT1 and CAATCH1: Orthologs to Understand Structure-Function Relationships in Mammalian SLC6 Transporters.Neurochemical research · 2022Article
- Molecular Mechanism of Nramp-Family Transition Metal Transport.Journal of molecular biology · 2021Review
- Article
- A non-helical region in transmembrane helix 6 of hydrophobic amino acid transporter MhsT mediates substrate recognition.The EMBO journal · 2021Article
- Heteromeric Solute Carriers: Function, Structure, Pathology and Pharmacology.Advances in experimental medicine and biology · 2021Review
- Expression dynamics of solute carrier family 15 member 4 (SLC15A4) and its potential regulatory role in ovarian development of the Indian white shrimp, Penaeus indicus.Molecular biology reports · 2020Article
- Mapping of Ion and Substrate Binding Sites in Human Sodium Iodide Symporter (hNIS).Journal of chemical information and modeling · 2020Article
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.