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Title: Structure and function of the divalent anion/Na+ symporter from Vibrio cholerae and a humanized variant

Journal Article · · Nature Communications
DOI:https://doi.org/10.1038/ncomms15009· OSTI ID:1368268
 [1];  [1];  [1];  [1];  [1]
  1. Rosalind Franklin Univ. of Medicine and Science, North Chicago, IL (United States)
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Integral membrane proteins of the divalent anion/Na+ symporter (DASS) family translocate dicarboxylate, tricarboxylate or sulphate across cell membranes, typically by utilizing the preexisting Na+ gradient. The molecular determinants for substrate recognition by DASS remain obscure, largely owing to the absence of any substrate-bound DASS structure. Here we present 2.8-Å resolution X-ray structures of VcINDY, a DASS from Vibrio cholerae that catalyses the co-transport of Na+ and succinate. These structures portray the Na+-bound VcINDY in complexes with succinate and citrate, elucidating the binding sites for substrate and two Na+ ions. Furthermore, we report the structures of a humanized variant of VcINDY in complexes with succinate and citrate, which predict how a human citrate-transporting DASS may interact with its bound substrate. Our findings provide insights into metabolite transport by DASS, establishing a molecular basis for future studies on the regulation of this transport process.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Organization:
National Institutes of Health (NIH)
Grant/Contract Number:
R01-GM094195
OSTI ID:
1368268
Journal Information:
Nature Communications, Vol. 8, Issue 1; ISSN 2041-1723
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
ENGLISH
Citation Metrics:
Cited by: 30 works
Citation information provided by
Web of Science

References (54)

Mechanism of Na+-dependent citrate transport from the structure of an asymmetrical CitS dimer journal December 2015
Structure of a prokaryotic fumarate transporter reveals the architecture of the SLC26 family journal September 2015
Principles of activation and permeation in an anion-selective Cys-loop receptor journal May 2011
Structural and functional significance of water permeation through cotransporters journal October 2016
Structural basis for dynamic mechanism of nitrate/nitrite antiport by NarK journal May 2015
Refinement of Macromolecular Structures by the Maximum-Likelihood Method journal May 1997
Structure and mechanism of a bacterial sodium-dependent dicarboxylate transporter journal October 2012
Validation of metal-binding sites in macromolecular structures with the CheckMyMetal web server journal December 2013
Succinate Complex Crystal Structures of the α-Ketoglutarate-dependent Dioxygenase AtsK: STERIC ASPECTS OF ENZYME SELF-HYDROXYLATION journal November 2004
Crystal structure of the Alcanivorax borkumensis YdaH transporter reveals an unusual topology journal April 2015
Structure and Mechanism of a Nitrate Transporter journal March 2013
Improved methods for building protein models in electron density maps and the location of errors in these models journal March 1991
Na+–sulfate cotransporter SLC13A1 journal November 2013
Structural basis for action by diverse antidepressants on biogenic amine transporters journal October 2013
Specificity of the transport system for tricarboxylic acid cycle intermediates in renal brush borders journal February 1980
C4-Dicarboxylates Sensing Mechanism Revealed by the Crystal Structures of DctB Sensor Domain journal October 2008
X-ray structure of a ClC chloride channel at 3.0 Å reveals the molecular basis of anion selectivity journal January 2002
The CCP4 suite programs for protein crystallography journal September 1994
Functional characterization and genomic organization of the human Na+-sulfate cotransporter hNaS2 gene (SLC13A4) journal January 2005
Electrogenic cotransport of Na+ and sulfate in Xenopus oocytes expressing the cloned Na+SO4(2-) transport protein NaSi-1. journal April 1994
Long-range electrostatic interaction in the bacterial photosynthetic reaction centre journal December 1995
Relevance of NAC-2, an Na+-coupled citrate transporter, to life span, body size and fat content in Caenorhabditis elegans journal April 2004
Valence Screening of Water in Protein Crystals Reveals Potential Na+Binding Sites journal February 1996
Functional features and genomic organization of mouse NaCT, a sodium-coupled transporter for tricarboxylic acid cycle intermediates journal March 2004
Coupled binding mechanism of three sodium ions and aspartate in the glutamate transporter homologue GltTk journal November 2016
Pushing the boundaries of molecular replacement with maximum likelihood journal September 2001
Identification and Characterization of the Dicarboxylate Uptake System DccT in Corynebacterium glutamicum journal July 2008
Metal–ligand geometry relevant to proteins and in proteins: sodium and potassium journal April 2002
Structure and Function of Neisseria gonorrhoeae MtrF Illuminates a Class of Antimetabolite Efflux Pumps journal April 2015
Long-lived Indy induces reduced mitochondrial reactive oxygen species production and oxidative damage journal January 2009
Structural and Functional Characteristics of Two Sodium-coupled Dicarboxylate Transporters (ceNaDC1 and ceNaDC2) from Caenorhabditis elegans and Their Relevance to Life Span journal December 2002
Functional characterization of a Na+-dependent dicarboxylate transporter from Vibrio cholerae journal May 2014
Snapshot of Antidepressants at Work: The Structure of Neurotransmitter Transporter Proteins journal April 2014
Crystal structure of a nitrate/nitrite exchanger journal May 2013
Crystal structure of a substrate-free aspartate transporter journal September 2013
Coupled ion binding and structural transitions along the transport cycle of glutamate transporters journal May 2014
The Yeast Mitochondrial Citrate Transport Protein: MOLECULAR DETERMINANTS OF ITS SUBSTRATE SPECIFICITY journal June 2010
Three-dimensional structure of carbamoyl phosphate and succinate bound to aspartate carbamoyltransferase. journal June 1988
Applications of the Sequence Rule. I. Naming the Paired Ligands g,g at a Tetrahedral Atom Xggij. II. Naming the Two Faces of a Trigonal Atom Yghi journal June 1966
The Renal Na+-Dependent Dicarboxylate Transporter, NaDC-3, Translocates Dimethyl- and Disulfhydryl-Compounds and Contributes to Renal Heavy Metal Detoxification journal November 2002
The ion transporter superfamily journal December 2003
Coupling substrate and ion binding to extracellular gate of a sodium-dependent aspartate transporter journal January 2007
Structure and insights into the function of a Ca2+-activated Cl− channel journal October 2014
The bacterial dicarboxylate transporter VcINDY uses a two-domain elevator-type mechanism journal February 2016
Functional Characterization of a Na+-Coupled Dicarboxylate Carrier Protein from Staphylococcus aureus journal July 2005
Deletion of the Mammalian INDY Homolog Mimics Aspects of Dietary Restriction and Protects against Adiposity and Insulin Resistance in Mice journal August 2011
Sodium-coupled dicarboxylate and citrate transporters from the SLC13 family journal October 2013
Crystal Structures of C 4 -Dicarboxylate Ligand Complexes with Sensor Domains of Histidine Kinases DcuS and DctB journal August 2008
Functional Reconstitution of SdcS, a Na+-Coupled Dicarboxylate Carrier Protein from Staphylococcus aureus journal November 2006
Electrostatic activation of Escherichia coli methionine repressor journal April 1994
Extended Life-Span Conferred by Cotransporter Gene Mutations in Drosophila journal December 2000
[20] Processing of X-ray diffraction data collected in oscillation mode book January 1997
Determinants of Substrate and Cation Transport in the Human Na + /Dicarboxylate Cotransporter NaDC3 journal May 2014
Functional characterization of a Na+-coupled dicarboxylate transporter from Bacillus licheniformis journal December 2009

Cited By (3)

Molecular Plasticity of the Nucleus Accumbens Revisited—Astrocytic Waves Shall Rise journal May 2019
SLC13A3 variants cause acute reversible leukoencephalopathy and α-ketoglutarate accumulation: SLC13A3 Variants journal January 2019
Substrate-dependent accessibility changes in the Na + -dependent C 4 -dicarboxylate transporter, VcINDY, suggest differential substrate effects in a multistep mechanism posted_content January 2020

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
Ion transport
Transporters
X-ray crystallography