8fho
From Proteopedia
(Difference between revisions)
| Line 5: | Line 5: | ||
<table><tr><td colspan='2'>[[8fho]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Danio_rerio Danio rerio] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8FHO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8FHO FirstGlance]. <br> | <table><tr><td colspan='2'>[[8fho]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Danio_rerio Danio rerio] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8FHO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8FHO FirstGlance]. <br> | ||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.95Å</td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.95Å</td></tr> | ||
| - | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=XZF:( | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=XZF:(3S)-6-chloro-2-methyl-1,1-dioxo-3-{[(2,2,2-trifluoroethyl)sulfanyl]methyl}-1,2,3,4-tetrahydro-1lambda~6~,2,4-benzothiadiazine-7-sulfonamide'>XZF</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=8fho FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8fho OCA], [https://pdbe.org/8fho PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8fho RCSB], [https://www.ebi.ac.uk/pdbsum/8fho PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8fho ProSAT]</span></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=8fho FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8fho OCA], [https://pdbe.org/8fho PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8fho RCSB], [https://www.ebi.ac.uk/pdbsum/8fho PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8fho ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| Line 16: | Line 16: | ||
The sodium-chloride cotransporter (NCC) is critical for kidney physiology(1). The NCC has a major role in salt reabsorption in the distal convoluted tubule of the nephron(2,3), and mutations in the NCC cause the salt-wasting disease Gitelman syndrome(4). As a key player in salt handling, the NCC regulates blood pressure and is the target of thiazide diuretics, which have been widely prescribed as first-line medications to treat hypertension for more than 60 years(5-7). Here we determined the structures of human NCC alone and in complex with a commonly used thiazide diuretic using cryo-electron microscopy. These structures, together with functional studies, reveal major conformational states of the NCC and an intriguing regulatory mechanism. They also illuminate how thiazide diuretics specifically interact with the NCC and inhibit its transport function. Our results provide critical insights for understanding the Na-Cl cotransport mechanism of the NCC, and they establish a framework for future drug design and for interpreting disease-related mutations. | The sodium-chloride cotransporter (NCC) is critical for kidney physiology(1). The NCC has a major role in salt reabsorption in the distal convoluted tubule of the nephron(2,3), and mutations in the NCC cause the salt-wasting disease Gitelman syndrome(4). As a key player in salt handling, the NCC regulates blood pressure and is the target of thiazide diuretics, which have been widely prescribed as first-line medications to treat hypertension for more than 60 years(5-7). Here we determined the structures of human NCC alone and in complex with a commonly used thiazide diuretic using cryo-electron microscopy. These structures, together with functional studies, reveal major conformational states of the NCC and an intriguing regulatory mechanism. They also illuminate how thiazide diuretics specifically interact with the NCC and inhibit its transport function. Our results provide critical insights for understanding the Na-Cl cotransport mechanism of the NCC, and they establish a framework for future drug design and for interpreting disease-related mutations. | ||
| - | + | , PMID:36792826<ref>PMID:36792826</ref> | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
Current revision
Cryo-EM structure of human NCC (class 1)
| |||||||||||
Categories: Danio rerio | Homo sapiens | Large Structures | Fan M | Feng L | Zhang J
