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- PDB-8y5u: human NaS1 intermediate state 1 -

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Basic information

Entry
Database: PDB / ID: 8y5u
Titlehuman NaS1 intermediate state 1
ComponentsSolute carrier family 13 member 1
KeywordsPROTEIN TRANSPORT / membrane sodium anion transporter
Function / homology
Function and homology information


sodium:sulfate symporter activity / monoatomic anion:sodium symporter activity / Sodium-coupled sulphate, di- and tri-carboxylate transporters / sulfate transmembrane transport / sodium ion transport / apical plasma membrane / plasma membrane
Similarity search - Function
Sodium/sulphate symporter, conserved site / Sodium:sulfate symporter family signature. / Sodium:sulfate symporter transmembrane region / Solute carrier family 13
Similarity search - Domain/homology
Solute carrier family 13 member 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.04 Å
AuthorsZhang, S.S.
Funding support China, 1items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)32030056 China
CitationJournal: Sci Adv / Year: 2024
Title: Structural basis for the reaction cycle and transport mechanism of human Na-sulfate cotransporter NaS1 (SLC13A1).
Authors: Xudong Chen / Youqi Zhang / Jian Yin / Chang Liu / Min Xie / Yixue Wang / Meiying Chen / Rui Zhang / Xinyi Yuan / De Li / Xiangmei Chen / Xin Gao / Guangyan Cai / Sensen Zhang / Boda Zhou / Maojun Yang /
Abstract: Sulfate (SO) is a pivotal inorganic anion with essential roles in mammalian physiology. NaS1, a member of solute carrier 13 family and divalent anion/sodium symporter family, functions as a Na- ...Sulfate (SO) is a pivotal inorganic anion with essential roles in mammalian physiology. NaS1, a member of solute carrier 13 family and divalent anion/sodium symporter family, functions as a Na-sulfate cotransporter, facilitating sulfate (re)absorption across renal proximal tubule and small intestine epithelia. While previous studies have linked several human disorders to mutations in the gene, its transport mechanism remains unclear. Here, we report the cryo-electron microscopy structures of five distinct conformations of the human NaS1 at resolutions of 2.7 to 3.3 angstroms, revealing the substrates recognition mechanism and the conformational change of NaS1 during the Na-sulfate cotransport cycle. Our studies delineate the molecular basis of the detailed dynamic transport cycle of NaS1. These findings advance the current understanding of the Na-sulfate cotransport mechanism, human sulfate (re)absorption, and the implications of disease-associated NaS1 mutations.
History
DepositionFeb 1, 2024Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Jan 22, 2025Provider: repository / Type: Initial release

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Assembly

Deposited unit
A: Solute carrier family 13 member 1
B: Solute carrier family 13 member 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)132,6317
Polymers132,3702
Non-polymers2615
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_5551

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Components

#1: Protein Solute carrier family 13 member 1 / Renal sodium/sulfate cotransporter / Na(+)/sulfate cotransporter / hNaSi-1


Mass: 66184.859 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: SLC13A1, NAS1, NASI1 / Cell line (production host): HEK293F / Production host: Homo sapiens (human) / References: UniProt: Q9BZW2
#2: Chemical ChemComp-NA / SODIUM ION


Mass: 22.990 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: Na
#3: Chemical ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: SO4
Has ligand of interestN
Has protein modificationN

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

ComponentName: membrane sodium anion transproter 1 / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Homo sapiens (human)
Buffer solutionpH: 7.2
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: TFS KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 2500 nm / Nominal defocus min: 1200 nm
Image recordingElectron dose: 50 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k)

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Processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.04 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 102182 / Symmetry type: POINT

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