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Yorodumi- PDB-7uv0: Structure of the sodium/iodide symporter (NIS) in complex with io... -
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-Basic information
Entry | Database: PDB / ID: 7uv0 | ||||||
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Title | Structure of the sodium/iodide symporter (NIS) in complex with iodide and sodium | ||||||
Components | Sodium/iodide cotransporter | ||||||
Keywords | TRANSPORT PROTEIN / NIS / iodide / symporter / cryo-EM | ||||||
Function / homology | Function and homology information sodium:iodide symporter activity / iodide transmembrane transport / Thyroxine biosynthesis / salt transmembrane transporter activity / cellular response to Thyroid stimulating hormone / Organic anion transporters / monoatomic anion:sodium symporter activity / iodide transmembrane transporter activity / iodide transport / cellular response to gonadotropin stimulus ...sodium:iodide symporter activity / iodide transmembrane transport / Thyroxine biosynthesis / salt transmembrane transporter activity / cellular response to Thyroid stimulating hormone / Organic anion transporters / monoatomic anion:sodium symporter activity / iodide transmembrane transporter activity / iodide transport / cellular response to gonadotropin stimulus / symporter activity / thyroid hormone generation / sodium ion transport / cellular response to cAMP / cellular response to forskolin / transmembrane transport / protein homodimerization activity / extracellular exosome / nucleus / plasma membrane / cytoplasm Similarity search - Function | ||||||
Biological species | Rattus norvegicus (Norway rat) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.1 Å | ||||||
Authors | Ravera, S. / Nicola, J.P. / Salazar-De Simone, G. / Sigworth, F. / Karakas, E. / Amzel, L.M. / Bianchet, M. / Carrasco, N. | ||||||
Funding support | United States, 1items
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Citation | Journal: Nature / Year: 2022 Title: Structural insights into the mechanism of the sodium/iodide symporter. Authors: Silvia Ravera / Juan Pablo Nicola / Glicella Salazar-De Simone / Fred J Sigworth / Erkan Karakas / L Mario Amzel / Mario A Bianchet / Nancy Carrasco / Abstract: The sodium/iodide symporter (NIS) is the essential plasma membrane protein that mediates active iodide (I) transport into the thyroid gland, the first step in the biosynthesis of the thyroid hormones- ...The sodium/iodide symporter (NIS) is the essential plasma membrane protein that mediates active iodide (I) transport into the thyroid gland, the first step in the biosynthesis of the thyroid hormones-the master regulators of intermediary metabolism. NIS couples the inward translocation of I against its electrochemical gradient to the inward transport of Na down its electrochemical gradient. For nearly 50 years before its molecular identification, NIS was the molecule at the centre of the single most effective internal radiation cancer therapy: radioiodide (I) treatment for thyroid cancer. Mutations in NIS cause congenital hypothyroidism, which must be treated immediately after birth to prevent stunted growth and cognitive deficiency. Here we report three structures of rat NIS, determined by single-particle cryo-electron microscopy: one with no substrates bound; one with two Na and one I bound; and one with one Na and the oxyanion perrhenate bound. Structural analyses, functional characterization and computational studies show the substrate-binding sites and key residues for transport activity. Our results yield insights into how NIS selects, couples and translocates anions-thereby establishing a framework for understanding NIS function-and how it transports different substrates with different stoichiometries and releases substrates from its substrate-binding cavity into the cytosol. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7uv0.cif.gz | 106 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7uv0.ent.gz | 80 KB | Display | PDB format |
PDBx/mmJSON format | 7uv0.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7uv0_validation.pdf.gz | 429.7 KB | Display | wwPDB validaton report |
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Full document | 7uv0_full_validation.pdf.gz | 433 KB | Display | |
Data in XML | 7uv0_validation.xml.gz | 11.2 KB | Display | |
Data in CIF | 7uv0_validation.cif.gz | 16.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/uv/7uv0 ftp://data.pdbj.org/pub/pdb/validation_reports/uv/7uv0 | HTTPS FTP |
-Related structure data
Related structure data | 26808MC 7uuyC 7uuzC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 73914.414 Da / Num. of mol.: 1 / Mutation: N225Q, N485Q and N497Q Source method: isolated from a genetically manipulated source Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Slc5a5, Nis / Production host: Homo sapiens (human) / References: UniProt: Q63008 | ||||||
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#2: Chemical | #3: Chemical | ChemComp-IOD / | #4: Chemical | ChemComp-3PH / | Has ligand of interest | Y | |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Sodium/iodide symporter / Type: COMPLEX / Details: In complex with iodide and sodium. / Entity ID: #1 / Source: RECOMBINANT | ||||||||||||||||||||||||||||||
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Molecular weight | Value: 0.075 MDa / Experimental value: NO | ||||||||||||||||||||||||||||||
Source (natural) | Organism: Rattus norvegicus (Norway rat) | ||||||||||||||||||||||||||||||
Source (recombinant) | Organism: Homo sapiens (human) / Cell: 293F | ||||||||||||||||||||||||||||||
Buffer solution | pH: 8 | ||||||||||||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 2 mg/ml / Embedding applied: YES / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES / Details: Protein was supplemented with 2 mM KI. | ||||||||||||||||||||||||||||||
Specimen support | Grid material: COPPER / Grid mesh size: 200 divisions/in. / Grid type: Quantifoil R1.2/1.3 | ||||||||||||||||||||||||||||||
EM embedding | Material: vitrified ice | ||||||||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 81000 X / Nominal defocus max: -0.24 nm / Nominal defocus min: -0.15 nm / Cs: 2.7 mm |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 45 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Num. of grids imaged: 2 |
-Processing
Software | Name: PHENIX / Version: 1.20.1_4487: / Classification: refinement | |||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | |||||||||||||||
3D reconstruction | Resolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 384418 / Symmetry type: POINT | |||||||||||||||
Atomic model building | Protocol: FLEXIBLE FIT / Space: REAL |