ArticleProceedings of the National Academy of Sciences of the United States of America2007
Identification of a chloride ion binding site in Na+/Cl -dependent transporters.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 125 papers.
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125 citing papers in PubMed, 200 citations in OpenAlex.
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- Substrate Binding and Conformational Dynamics of the Monoamine Transporters.Advances in neurobiology · 2025Review
- Cryo-EM structures of the human band 3 transporter indicate a transport mechanism involving the coupled movement of chloride and bicarbonate ions.PLoS biology · 2024Article
- Identification of the potassium-binding site in serotonin transporter.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Exploring the KeLife · 2024Article
- Unique Substrate Recognition and Sodium-Substrate Binding Stoichiometry in a Bacterial Serotonin Transporter, TuriSERT.International journal of molecular sciences · 2023Article
- Molecular basis for substrate recognition and transport of human GABA transporter GAT1.Nature structural & molecular biology · 2023Article
- A comparative review on the well-studied GAT1 and the understudied BGT-1 in the brain.Frontiers in physiology · 2023Review
- The "www" ofMembranes · 2022Review
- Determining Ligand and Ion-Induced Conformational Changes in Serotonin Transporter with Its Fluorescent Substrates.International journal of molecular sciences · 2022Article
- Two Lignan Glycosides fromPharmaceuticals (Basel, Switzerland) · 2022Article
- The substrate import mechanism of the human serotonin transporter.Biophysical journal · 2022Article
- Forty Four Years With Baruch Kanner and The Chloride Ion.Neurochemical research · 2022Article
- Reconstitution of GABA, Glycine and Glutamate Transporters.Neurochemical research · 2022Review
- Molecular Basis of Coupled Transport and Anion Conduction in Excitatory Amino Acid Transporters.Neurochemical research · 2022Review
- The Lepidopteran KAAT1 and CAATCH1: Orthologs to Understand Structure-Function Relationships in Mammalian SLC6 Transporters.Neurochemical research · 2022Article
- Assessment of Paroxetine Molecular Interactions with Selected Monoamine and γ-Aminobutyric Acid Transporters.International journal of molecular sciences · 2021Article
65 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The recent determination of the crystal structure of the leucine transporter from Aquifex aeolicus (aaLeuT) has provided significant insights into the function of neurotransmitter:sodium symporters. Transport by aaLeuT is Cl(-) independent, whereas many neurotransmitter:sodium symporters from higher organisms depend on Cl(-) ions. However, the only Cl(-) ion identified in the aaLeuT structure interacts with nonconserved residues in extracellular loops, and thus the relevance of this binding site is unclear. Here, we use calculations of pK(A)s and homology modeling to predict the location of a functionally important Cl(-) binding site in serotonin transporter and other Cl(-)-dependent transporters. We validate our model through the site-directed mutagenesis of residues predicted to coordinate the Cl(-) ion and through the observation of sequence conservation patterns in other Cl(-)-dependent transporters. The proposed site is located midway across the membrane and is formed by residues from transmembrane helices 2, 6, and 7. It is close to the Na1 sodium binding site, thus providing an explanation for the coupling of Cl(-) and Na(+) ions during transport. Other implications of the model are also discussed.
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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.