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- EMDB-26807: Structure of the sodium/iodide symporter (NIS) in complex with pe... -
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Open data
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Basic information
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Title | Structure of the sodium/iodide symporter (NIS) in complex with perrhenate and sodium | |||||||||
![]() | Sharpened map after local refinement. | |||||||||
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![]() | NIS / iodide / symporter / cryo-EM / TRANSPORT PROTEIN | |||||||||
Function / homology | ![]() sodium:iodide symporter activity / iodide transmembrane transport / Thyroxine biosynthesis / 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 ...sodium:iodide symporter activity / iodide transmembrane transport / Thyroxine biosynthesis / 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 / nucleus / plasma membrane / cytoplasm Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.2 Å | |||||||||
![]() | Ravera S / Nicola JP / Salazar-De Simone G / Sigworth F / Karakas E / Amzel LM / Bianchet M / Carrasco N | |||||||||
Funding support | ![]()
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![]() | ![]() 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
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 85.6 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 20.5 KB 20.5 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 10.8 KB | Display | ![]() |
Images | ![]() | 79.6 KB | ||
Masks | ![]() | 91.1 MB | ![]() | |
Filedesc metadata | ![]() | 6.6 KB | ||
Others | ![]() ![]() ![]() | 43.7 MB 83.8 MB 83.8 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 723.7 KB | Display | ![]() |
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Full document | ![]() | 723.2 KB | Display | |
Data in XML | ![]() | 17.7 KB | Display | |
Data in CIF | ![]() | 22.6 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7uuzMC ![]() 7uuyC ![]() 7uv0C M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Map
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Annotation | Sharpened map after local refinement. | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.068 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
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Density Histograms |
-Additional map: Unsharpened map after local refinement.
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Annotation | Unsharpened map after local refinement. | ||||||||||||
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-Half map: #2
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Density Histograms |
-Half map: #1
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Density Histograms |
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Sample components
-Entire : Sodium/iodide symporter
Entire | Name: Sodium/iodide symporter |
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Components |
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-Supramolecule #1: Sodium/iodide symporter
Supramolecule | Name: Sodium/iodide symporter / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 / Details: In complex with perrhenate and sodium. |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 75 KDa |
-Macromolecule #1: Sodium/iodide cotransporter
Macromolecule | Name: Sodium/iodide cotransporter / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 73.914414 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MYPYDVPDYA ENLYFQSEGA EAGARATFGA WDYGVFATML LVSTGIGLWV GLARGGQRSA DDFFTGGRQL AAVPVGLSLA ASFMSAVQV LGVPAEAARY GLKFLWMCAG QLLNSLLTAF LFLPIFYRLG LTSTYQYLEL RFSRAVRLCG TLQYLVATML Y TGIVIYAP ...String: MYPYDVPDYA ENLYFQSEGA EAGARATFGA WDYGVFATML LVSTGIGLWV GLARGGQRSA DDFFTGGRQL AAVPVGLSLA ASFMSAVQV LGVPAEAARY GLKFLWMCAG QLLNSLLTAF LFLPIFYRLG LTSTYQYLEL RFSRAVRLCG TLQYLVATML Y TGIVIYAP ALILNQVTGL DIWASLLSTG IICTLYTTVG GMKAVVWTDV FQVVVMLVGF WVILARGVIL LGGPRNVLSL AQ QHSRINL MDFDPDPRSR YTFWTFIVGG TLVWLSMYGV NQAQVQRYVA CHTEGKAKLA LLVNQLGLFL IVASAACCGI VMF VYYKDC DPLLTGRISA PDQYMPLLVL DIFEDLPGVP GLFLACAYSG TLSTASTSIN AMAAVTVEDL IKPRMPGLAP RKLV FISKG LSFIYGSACL TVAALSSLLG GGVLQGSFTV MGVISGPLLG AFTLGMLLPA CNTPGVLSGL AAGLAVSLWV AVGAT LYPP GEQTMGVLPT SAAGCTQDSV LLGPPGATQA SNGIPSSGMD TGRPALADTF YAISYLYYGA LGTLTTMLCG ALISYL TGP TKRSSLGPGL LWWDLARQTA SVAPKEDTAT LEESLVKGPE DIPAVTKKPP GLKPGAETHP LYLGHDVETN LSGGGGA LE VLFQGPHHHH HHHHMDEKTT GWRGGHVVEG LAGELEQLRA RLEHHPQGQR EP UniProtKB: Sodium/iodide cotransporter |
-Macromolecule #2: SODIUM ION
Macromolecule | Name: SODIUM ION / type: ligand / ID: 2 / Number of copies: 1 |
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Molecular weight | Theoretical: 22.99 Da |
-Macromolecule #3: PERRHENATE
Macromolecule | Name: PERRHENATE / type: ligand / ID: 3 / Number of copies: 1 / Formula: REO |
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Molecular weight | Theoretical: 250.205 Da |
Chemical component information | ![]() ChemComp-REO: |
-Macromolecule #4: 1,2-DIACYL-GLYCEROL-3-SN-PHOSPHATE
Macromolecule | Name: 1,2-DIACYL-GLYCEROL-3-SN-PHOSPHATE / type: ligand / ID: 4 / Number of copies: 1 / Formula: 3PH |
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Molecular weight | Theoretical: 704.998 Da |
Chemical component information | ![]() ChemComp-3PH: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 2 mg/mL | ||||||||||||||||||
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Buffer | pH: 8 Component:
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Sugar embedding | Material: vitrified ice | ||||||||||||||||||
Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 200 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE | ||||||||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV | ||||||||||||||||||
Details | Protein was supplemented with 1 mM Sodium Perrhenate |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Number grids imaged: 2 / Average electron dose: 45.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: -0.00024 µm / Nominal defocus min: -0.00015 µm / Nominal magnification: 81000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
-Atomic model buiding 1
Refinement | Space: REAL / Protocol: FLEXIBLE FIT |
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Output model | ![]() PDB-7uuz: |