ArticleProceedings of the National Academy of Sciences of the United States of America2013
Arginine oscillation explains Na+ independence in the substrate/product antiporter CaiT.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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20 citing papers in PubMed, 23 citations in OpenAlex.
- Structural insights into bacterial dimethylsulfoniopropionate import by BCCT-family transporters.The EMBO journal · 2026Article
- Cryo-EM structures reveal the HLife science alliance · 2025Article
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- Structure and mechanism of the osmoregulated choline transporter BetT.Science advances · 2024Article
- Review
- Cryo-EM structure of the human NKCC1 transporter reveals mechanisms of ion coupling and specificity.The EMBO journal · 2022Article
- Prokaryotic Solute/Sodium Symporters: Versatile Functions and Mechanisms of a Transporter Family.International journal of molecular sciences · 2021Review
- Article
- Mapping of Ion and Substrate Binding Sites in Human Sodium Iodide Symporter (hNIS).Journal of chemical information and modeling · 2020Article
- Locking Two Rigid-body Bundles in an Outward-Facing Conformation: The Ion-coupling Mechanism in a LeuT-fold Transporter.Scientific reports · 2019Article
- L amino acid transporter structure and molecular bases for the asymmetry of substrate interaction.Nature communications · 2019Article
- A novel proton transfer mechanism in the SLC11 family of divalent metal ion transporters.Scientific reports · 2017Article
- Arginine substitution of a cysteine in transmembrane helix M8 converts Na+,K+-ATPase to an electroneutral pump similar to H+,K+-ATPase.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Asymmetry in inward- and outward-affinity constant of transport explain unidirectional lysine flux in Saccharomyces cerevisiae.Scientific reports · 2016Article
- A giant molecular proton pump: structure and mechanism of respiratory complex I.Nature reviews. Molecular cell biology · 2015Review
- Carnitine in bacterial physiology and metabolism.Microbiology (Reading, England) · 2015Review
- Identification of a second substrate-binding site in solute-sodium symporters.The Journal of biological chemistry · 2015Article
- Article
- Substrate-bound outward-open state of the betaine transporter BetP provides insights into Na+ coupling.Nature communications · 2014Article
- Article
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3 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Most secondary-active transporters transport their substrates using an electrochemical ion gradient. In contrast, the carnitine transporter (CaiT) is an ion-independent, l-carnitine/γ-butyrobetaine antiporter belonging to the betaine/carnitine/choline transporter family of secondary transporters. Recently determined crystal structures of CaiT from Escherichia coli and Proteus mirabilis revealed an inverted five-transmembrane-helix repeat similar to that in the amino acid/Na(+) symporter LeuT. The ion independence of CaiT makes it unique in this family. Here we show that mutations of arginine 262 (R262) make CaiT Na(+)-dependent. The transport activity of R262 mutants increased by 30-40% in the presence of a membrane potential, indicating substrate/Na(+) cotransport. Structural and biochemical characterization revealed that R262 plays a crucial role in substrate binding by stabilizing the partly unwound TM1' helix. Modeling CaiT from P. mirabilis in the outward-open and closed states on the corresponding structures of the related symporter BetP reveals alternating orientations of the buried R262 sidechain, which mimic sodium binding and unbinding in the Na(+)-coupled substrate symporters. We propose that a similar mechanism is operative in other Na(+)/H(+)-independent transporters, in which a positively charged amino acid replaces the cotransported cation. The oscillation of the R262 sidechain in CaiT indicates how a positive charge triggers the change between outward-open and inward-open conformations as a unifying critical step in LeuT-type transporters.
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