ArticleNature2012
Structure and mechanism of a bacterial sodium-dependent dicarboxylate transporter.
Article in Nature, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers.
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Who cites it
118 citing papers in PubMed, 192 citations in OpenAlex.
- Structures of the human sodium-citrate cotransporter NaCT with and without substrates.Structure (London, England : 1993) · 2026Article
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- Structures of the human sodium-citrate cotransporter NaCT with and without substrates.bioRxiv : the preprint server for biology · 2026Article
- Functional role of a structural water in the elevator domain of dicarboxylate transporter VcINDY.PNAS nexus · 2026Article
- Structural basis of metalloid transport by the arsenite efflux pump ArsB.Nature communications · 2026Article
- Discovery and Characterization of a Nonacidic Small-Molecule Inhibitor of the Sodium-Coupled Dicarboxylate Transporter NaCT.Journal of medicinal chemistry · 2026Article
- Elevator mechanism dynamics in a sodium-coupled dicarboxylate transporter.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Memorization bias impacts modeling of alternative conformational states of solute carrier membrane proteins with methods from deep learning.PLoS computational biology · 2025Article
- Elucidation of the structure and molecular mechanisms of the aspartate antiporter.Communications biology · 2025Article
- A new class of binding-protein dependent solute transporter exemplified by the TAXI-GltS system from Bordetella pertussis.Communications biology · 2025Article
- Memorization Bias Impacts Modeling of Alternative Conformational States of Symmetric Solute Carrier Membrane Proteins with Methods from Deep Learning.bioRxiv : the preprint server for biology · 2025Article
- Structure-based modeling and engineering of Corynebacterium glutamicum LysE transporter for efficient extrusion of L-arginine.Communications biology · 2025Article
- Substrate translocation and inhibition in human dicarboxylate transporter NaDC3.Nature structural & molecular biology · 2025Article
- Molecular determinants of Neu5Ac binding to a tripartite ATP independent periplasmic (TRAP) transporter.eLife · 2025Article
- Identifying Opportunity Targets in Gram-Negative Pathogens for Infectious Disease Mitigation.ACS central science · 2025Review
- Structure and selectivity of a glutamate-specific TAXI TRAP binding protein from Vibrio cholerae.The Journal of general physiology · 2024Article
- Structural basis for the reaction cycle and transport mechanism of human NaScience advances · 2024Article
- Molecular Phenotypes Segregate Missense Mutations in SLC13A5 Epilepsy.Journal of molecular biology · 2024Article
- Article
- Interdomain-linkers control conformational transitions in the SLC23 elevator transporter UraA.Nature communications · 2024Article
58 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
In human cells, cytosolic citrate is a chief precursor for the synthesis of fatty acids, triacylglycerols, cholesterol and low-density lipoprotein. Cytosolic citrate further regulates the energy balance of the cell by activating the fatty-acid-synthesis pathway while downregulating both the glycolysis and fatty-acid β-oxidation pathways. The rate of fatty-acid synthesis in liver and adipose cells, the two main tissue types for such synthesis, correlates directly with the concentration of citrate in the cytosol, with the cytosolic citrate concentration partially depending on direct import across the plasma membrane through the Na(+)-dependent citrate transporter (NaCT). Mutations of the homologous fly gene (Indy; I'm not dead yet) result in reduced fat storage through calorie restriction. More recently, Nact (also known as Slc13a5)-knockout mice have been found to have increased hepatic mitochondrial biogenesis, higher lipid oxidation and energy expenditure, and reduced lipogenesis, which taken together protect the mice from obesity and insulin resistance. To understand the transport mechanism of NaCT and INDY proteins, here we report the 3.2 Å crystal structure of a bacterial INDY homologue. One citrate molecule and one sodium ion are bound per protein, and their binding sites are defined by conserved amino acid motifs, forming the structural basis for understanding the specificity of the transporter. Comparison of the structures of the two symmetrical halves of the transporter suggests conformational changes that propel substrate translocation.
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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.