7uv0: Difference between revisions
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==Structure of the sodium/iodide symporter (NIS) in complex with iodide and sodium== | |||
<StructureSection load='7uv0' size='340' side='right'caption='[[7uv0]], [[Resolution|resolution]] 3.10Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7uv0]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7UV0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UV0 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3PH:1,2-DIACYL-GLYCEROL-3-SN-PHOSPHATE'>3PH</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7uv0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7uv0 OCA], [https://pdbe.org/7uv0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7uv0 RCSB], [https://www.ebi.ac.uk/pdbsum/7uv0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7uv0 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/SC5A5_RAT SC5A5_RAT] Sodium:iodide symporter that mediates the transport of iodide into the thyroid gland (PubMed:8559252, PubMed:9341168, PubMed:32084174). Can also mediate the transport of chlorate, thiocynate, nitrate and selenocynate (PubMed:9341168).<ref>PMID:32084174</ref> <ref>PMID:8559252</ref> <ref>PMID:9341168</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
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(1,2). For nearly 50 years before its molecular identification(3), NIS was the molecule at the centre of the single most effective internal radiation cancer therapy: radioiodide ((131)I(-)) treatment for thyroid cancer(2). Mutations in NIS cause congenital hypothyroidism, which must be treated immediately after birth to prevent stunted growth and cognitive deficiency(2). 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. | |||
Structural insights into the mechanism of the sodium/iodide symporter.,Ravera S, Nicola JP, Salazar-De Simone G, Sigworth FJ, Karakas E, Amzel LM, Bianchet MA, Carrasco N Nature. 2022 Dec 14. doi: 10.1038/s41586-022-05530-2. PMID:36517601<ref>PMID:36517601</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 7uv0" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Rattus norvegicus]] | |||
[[Category: Amzel LM]] | |||
[[Category: Bianchet M]] | |||
[[Category: Carrasco N]] | |||
[[Category: Karakas E]] | |||
[[Category: Nicola JP]] | |||
[[Category: Ravera S]] | |||
[[Category: Salazar-De Simone G]] | |||
[[Category: Sigworth F]] | |||
Revision as of 12:22, 21 December 2022
Structure of the sodium/iodide symporter (NIS) in complex with iodide and sodiumStructure of the sodium/iodide symporter (NIS) in complex with iodide and sodium
Structural highlights
FunctionSC5A5_RAT Sodium:iodide symporter that mediates the transport of iodide into the thyroid gland (PubMed:8559252, PubMed:9341168, PubMed:32084174). Can also mediate the transport of chlorate, thiocynate, nitrate and selenocynate (PubMed:9341168).[1] [2] [3] Publication Abstract from PubMedThe 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(1,2). For nearly 50 years before its molecular identification(3), NIS was the molecule at the centre of the single most effective internal radiation cancer therapy: radioiodide ((131)I(-)) treatment for thyroid cancer(2). Mutations in NIS cause congenital hypothyroidism, which must be treated immediately after birth to prevent stunted growth and cognitive deficiency(2). 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. Structural insights into the mechanism of the sodium/iodide symporter.,Ravera S, Nicola JP, Salazar-De Simone G, Sigworth FJ, Karakas E, Amzel LM, Bianchet MA, Carrasco N Nature. 2022 Dec 14. doi: 10.1038/s41586-022-05530-2. PMID:36517601[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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