ArticleThe Journal of biological chemistry2011
Reconstructing a chloride-binding site in a bacterial neurotransmitter transporter homologue.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 34 citations in OpenAlex.
- Identification of the potassium-binding site in serotonin transporter.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Unique Substrate Recognition and Sodium-Substrate Binding Stoichiometry in a Bacterial Serotonin Transporter, TuriSERT.International journal of molecular sciences · 2023Article
- Reshaping the Binding Pocket of the Neurotransmitter:Solute Symporter (NSS) Family Transporter SLC6A14 (ATBBiomolecules · 2022Article
- The Lepidopteran KAAT1 and CAATCH1: Orthologs to Understand Structure-Function Relationships in Mammalian SLC6 Transporters.Neurochemical research · 2022Article
- Forty Four Years With Baruch Kanner and The Chloride Ion.Neurochemical research · 2022Article
- Chloride-dependent conformational changes in the GlyT1 glycine transporter.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Modeling and Simulation ofComputational and structural biotechnology journal · 2019Article
- Article
- A SLC6 transporter cloned from the lion's mane jellyfish (Cnidaria, Scyphozoa) is expressed in neurons.PloS one · 2019Article
- Neuropsychiatric disease-associated genetic variants of the dopamine transporter display heterogeneous molecular phenotypes.The Journal of biological chemistry · 2018Article
- Threonine 67 is a key component in the coupling of the NSS amino acid transporter KAAT1.Biochimica et biophysica acta. Biomembranes · 2018Article
- Conformational Dynamics on the Extracellular Side of LeuT Controlled by Na+ and K+ Ions and the Protonation State of Glu290.The Journal of biological chemistry · 2016Article
- Two Na+ Sites Control Conformational Change in a Neurotransmitter Transporter Homolog.The Journal of biological chemistry · 2016Article
- Microseconds simulations reveal a new sodium-binding site and the mechanism of sodium-coupled substrate uptake by LeuT.The Journal of biological chemistry · 2015Article
- Structural insights into the human RyR2 N-terminal region involved in cardiac arrhythmias.Acta crystallographica. Section D, Biological crystallography · 2014Article
- Chloride sensing by WNK1 involves inhibition of autophosphorylation.Science signaling · 2014Article
- The two Na+ sites in the human serotonin transporter play distinct roles in the ion coupling and electrogenicity of transport.The Journal of biological chemistry · 2014Article
- SLC1 glutamate transporters.Pflugers Archiv : European journal of physiology · 2014Review
- Article
- Chloride binding site of neurotransmitter sodium symporters.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
In ion-coupled transport proteins, occupation of selective ion-binding sites is required to trigger conformational changes that lead to substrate translocation. Neurotransmitter transporters, targets of abused and therapeutic drugs, require Na(+) and Cl(-) for function. We recently proposed a chloride-binding site in these proteins not present in Cl(-)-independent prokaryotic homologues. Here we describe conversion of the Cl(-)-independent prokaryotic tryptophan transporter TnaT to a fully functional Cl(-)-dependent form by a single point mutation, D268S. Mutations in TnaT-D268S, in wild type TnaT and in serotonin transporter provide direct evidence for the involvement of each of the proposed residues in Cl(-) coordination. In both SERT and TnaT-D268S, Cl(-) and Na(+) mutually increased each other's potency, consistent with electrostatic interaction through adjacent binding sites. These studies establish the site where Cl(-) binds to trigger conformational change during neurotransmitter transport.
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Registered trials
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.