ArticleThe Journal of biological chemistry2016
Two Na+ Sites Control Conformational Change in a Neurotransmitter Transporter Homolog.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
54 citing papers in PubMed.
- Cytosolic KJournal of chemical theory and computation · 2026Article
- Structural basis of vilazodone dual binding mode to the serotonin transporter.Nature communications · 2025Article
- Control of Conformational Transitions by the Conserved GXInternational journal of molecular sciences · 2025Article
- Exploring the Structural Dynamics of LeuT Using EPR Spectroscopy: A Focus on Transmembrane Helix 10.Journal of neurochemistry · 2025Article
- The conserved lysine residue in transmembrane helix 5 is pivotal for the cytoplasmic gating of the L-amino acid transporters.PNAS nexus · 2025Article
- Substrate Binding and Conformational Dynamics of the Monoamine Transporters.Advances in neurobiology · 2025Review
- Monitoring conformational changes in the human neurotransmitter transporter homologue LeuT withJournal of neurochemistry · 2025Article
- Molecular mechanisms and computational insights into human SGLTs: advancing toward selective SGLT1 inhibition.Frontiers in molecular biosciences · 2025Review
- Fluorescent non-canonical amino acid provides insight into the human serotonin transporter.Nature communications · 2024Article
- Article
- 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
- Cryo-EM structure of GABA transporter 1 reveals substrate recognition and transport mechanism.Nature structural & molecular biology · 2023Article
- Structure-based discovery of conformationally selective inhibitors of the serotonin transporter.Cell · 2023Article
- Cryo-EM structure of the human NKCC1 transporter reveals mechanisms of ion coupling and specificity.The EMBO journal · 2022Article
- Determining Ligand and Ion-Induced Conformational Changes in Serotonin Transporter with Its Fluorescent Substrates.International journal of molecular sciences · 2022Article
- Forty Four Years With Baruch Kanner and The Chloride Ion.Neurochemical research · 2022Article
- The Lepidopteran KAAT1 and CAATCH1: Orthologs to Understand Structure-Function Relationships in Mammalian SLC6 Transporters.Neurochemical research · 2022Article
- Molecular basis for redox control by the human cystine/glutamate antiporter system xcNature communications · 2021Article
- Rush Hour of LATs towards Their Transport Cycle.Membranes · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors.
Funding
Abstract
In LeuT, a prokaryotic homolog of neurotransmitter transporters, Na(+) stabilizes outward-open conformational states. We examined how each of the two LeuT Na(+) binding sites contributes to Na(+)-dependent closure of the cytoplasmic pathway using biochemical and biophysical assays of conformation. Mutating either of two residues that contribute to the Na2 site completely prevented cytoplasmic closure in response to Na(+), suggesting that Na2 is essential for this conformational change, whereas Na1 mutants retained Na(+) responsiveness. However, mutation of Na1 residues also influenced the Na(+)-dependent conformational change in ways that varied depending on the position mutated. Computational analyses suggest those mutants influence the ability of Na1 binding to hydrate the substrate pathway and perturb an interaction network leading to the extracellular gate. Overall, the results demonstrate that occupation of Na2 stabilizes outward-facing conformations presumably through a direct interaction between Na(+) and transmembrane helices 1 and 8, whereas Na(+) binding at Na1 influences conformational change through a network of intermediary interactions. The results also provide evidence that N-terminal release and helix motions represent distinct steps in cytoplasmic pathway opening.
Indexed as
Identifiers
What OpenQuestion holds
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.