ArticleNature structural & molecular biology2012
Experimental conditions can obscure the second high-affinity site in LeuT.
Article in Nature structural & molecular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 90 citations in OpenAlex.
- Exploring the Structural Dynamics of LeuT Using EPR Spectroscopy: A Focus on Transmembrane Helix 10.Journal of neurochemistry · 2025Article
- Alternating access of a bacterial homolog of neurotransmitter: sodium symporters determined from AlphaFold2 ensembles and DEER spectroscopy.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Prokaryotic Solute/Sodium Symporters: Versatile Functions and Mechanisms of a Transporter Family.International journal of molecular sciences · 2021Review
- Glycine Transporter 2: Mechanism and Allosteric Modulation.Frontiers in molecular biosciences · 2021Review
- Stoichiometric analysis of protein complexes by cell fusion and single molecule imaging.Scientific reports · 2020Article
- Identification of a New Allosteric Binding Site for Cocaine in Dopamine Transporter.Journal of chemical information and modeling · 2020Article
- Reconstitution of Membrane Proteins into Platforms Suitable for Biophysical and Structural Analyses.Methods in molecular biology (Clifton, N.J.) · 2020Article
- Article
- Monoamine transporters: structure, intrinsic dynamics and allosteric regulation.Nature structural & molecular biology · 2019Review
- Clickable photoaffinity ligands for the human serotonin transporter based on the selective serotonin reuptake inhibitor (S)-citalopram.Bioorganic & medicinal chemistry letters · 2018Article
- Structural elements required for coupling ion and substrate transport in the neurotransmitter transporter homolog LeuT.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- The LeuT-fold neurotransmitter:sodium symporter MhsT has two substrate sites.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Lipid bilayer composition modulates the unfolding free energy of a knotted α-helical membrane protein.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- A partially-open inward-facing intermediate conformation of LeuT is associated with NaNature communications · 2018Article
- Article
- The unexpected structures of hepatitis C virus envelope proteins.Experimental and therapeutic medicine · 2017Article
- Conformational dynamics of a neurotransmitter:sodium symporter in a lipid bilayer.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Direct assessment of substrate binding to the Neurotransmitter:Sodium Symporter LeuT by solid state NMR.eLife · 2017Article
- A Markov State-based Quantitative Kinetic Model of Sodium Release from the Dopamine Transporter.Scientific reports · 2017Article
- The external gate of the human and Drosophila serotonin transporters requires a basic/acidic amino acid pair for 3,4-methylenedioxymethamphetamine (MDMA) translocation and the induction of substrate efflux.Biochemical pharmacology · 2016Article
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5 authors at 2 institutions in 1 country.
Funding
Abstract
Neurotransmitter:Na(+) symporters (NSSs), the targets of antidepressants and psychostimulants, recapture neurotransmitters from the synapse in a Na(+)-dependent symport mechanism. The crystal structure of the NSS homolog LeuT from Aquifex aeolicus revealed one leucine substrate in an occluded, centrally located (S1) binding site next to two Na(+) ions. Computational studies combined with binding and flux experiments identified a second substrate (S2) site and a molecular mechanism of Na(+)-substrate symport that depends upon the allosteric interaction of substrate molecules in the two high-affinity sites. Here we show that the S2 site, which has not yet been identified by crystallographic approaches, can be blocked during preparation of detergent-solubilized LeuT, thereby obscuring its crucial role in Na(+)-coupled symport. This finding points to the need for caution in selecting experimental environments in which the properties and mechanistic features of membrane proteins can be delineated.
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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.