7yg1

From Proteopedia

(Difference between revisions)

Current revision

Cryo-EM structure of the C-terminal domain of the human sodium-chloride cotransporter

Structural highlights

7yg1 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.77Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

S12A3_HUMAN Gitelman syndrome. The disease is caused by variants affecting the gene represented in this entry.

Function

S12A3_HUMAN Electroneutral sodium and chloride ion cotransporter, which acts as a key mediator of sodium and chloride reabsorption in kidney distal convoluted tubules (PubMed:18270262, PubMed:21613606, PubMed:22009145, PubMed:36351028, PubMed:36792826). Also acts as a receptor for the pro-inflammatory cytokine IL18, thereby contributing to IL18-induced cytokine production, including IFNG, IL6, IL18 and CCL2 (By similarity). May act either independently of IL18R1, or in a complex with IL18R1 (By similarity).[UniProtKB:P59158]^[1] ^[2] ^[3] ^[4] ^[5]

Publication Abstract from PubMed

The sodium-chloride cotransporter NCC mediates the coupled import of sodium and chloride across the plasma membrane, playing vital roles in kidney extracellular fluid volume and blood pressure control. Here, we present the full-length structure of human NCC, with 2.9 A for the transmembrane domain and 3.8 A for the carboxyl-terminal domain. NCC adopts an inward-open conformation and a domain-swap dimeric assembly. Conserved ion binding sites among the cation-chloride cotransporters and the Na2 site are observed in our structure. A unique His residue in the substrate pocket in NCC potentially interacts with Na1 and Cl1 and might also mediate the coordination of Na2 through a Ser residue. Putative observed water molecules are indicated to participate in the coordination of ions and TM coupling. Together with transport activity assays, our structure provides the first glimpse of NCC and defines ion binding sites, promoting drug development for hypertension targeting on NCC.

Cryo-EM structure of the human sodium-chloride cotransporter NCC.,Nan J, Yuan Y, Yang X, Shan Z, Liu H, Wei F, Zhang W, Zhang Y Sci Adv. 2022 Nov 11;8(45):eadd7176. doi: 10.1126/sciadv.add7176. Epub 2022 Nov , 9. PMID:36351028^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Richardson C, Rafiqi FH, Karlsson HK, Moleleki N, Vandewalle A, Campbell DG, Morrice NA, Alessi DR. Activation of the thiazide-sensitive Na+-Cl kinases SPAK and OSR1. J Cell Sci. 2008 Mar 1;121(Pt 5):675-84. PMID:18270262 doi:10.1242/jcs.025312
↑ Cruz-Rangel S, Melo Z, Vazquez N, Meade P, Bobadilla NA, Pasantes-Morales H, Gamba G, Mercado A. Similar effects of all WNK3 variants on SLC12 cotransporters. Am J Physiol Cell Physiol. 2011 Sep;301(3):C601-8. doi:, 10.1152/ajpcell.00070.2011. Epub 2011 May 25. PMID:21613606 doi:http://dx.doi.org/10.1152/ajpcell.00070.2011
↑ Glaudemans B, Yntema HG, San-Cristobal P, Schoots J, Pfundt R, Kamsteeg EJ, Bindels RJ, Knoers NV, Hoenderop JG, Hoefsloot LH. Novel NCC mutants and functional analysis in a new cohort of patients with Gitelman syndrome. Eur J Hum Genet. 2012 Mar;20(3):263-70. doi: 10.1038/ejhg.2011.189. Epub 2011 Oct , 19. PMID:22009145 doi:http://dx.doi.org/10.1038/ejhg.2011.189
↑ Nan J, Yuan Y, Yang X, Shan Z, Liu H, Wei F, Zhang W, Zhang Y. Cryo-EM structure of the human sodium-chloride cotransporter NCC. Sci Adv. 2022 Nov 11;8(45):eadd7176. doi: 10.1126/sciadv.add7176. Epub 2022 Nov , 9. PMID:36351028 doi:http://dx.doi.org/10.1126/sciadv.add7176
↑ Fan M, Zhang J, Lee CL, Zhang J, Feng L. Structure and thiazide inhibition mechanism of the human Na-Cl cotransporter. Nature. 2023 Feb;614(7949):788-793. PMID:36792826 doi:10.1038/s41586-023-05718-0
↑ Nan J, Yuan Y, Yang X, Shan Z, Liu H, Wei F, Zhang W, Zhang Y. Cryo-EM structure of the human sodium-chloride cotransporter NCC. Sci Adv. 2022 Nov 11;8(45):eadd7176. doi: 10.1126/sciadv.add7176. Epub 2022 Nov , 9. PMID:36351028 doi:http://dx.doi.org/10.1126/sciadv.add7176

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/7yg1"

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[7yg1]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7YG1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7YG1 FirstGlance]. <br>
-</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=7yg1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7yg1 OCA], [https://pdbe.org/7yg1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7yg1 RCSB], [https://www.ebi.ac.uk/pdbsum/7yg1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7yg1 ProSAT]</span></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]] 3.77&#8491;</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=7yg1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7yg1 OCA], [https://pdbe.org/7yg1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7yg1 RCSB], [https://www.ebi.ac.uk/pdbsum/7yg1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7yg1 ProSAT]</span></td></tr>
 </table>
 == Disease ==
 [https://www.uniprot.org/uniprot/S12A3_HUMAN S12A3_HUMAN] Gitelman syndrome. The disease is caused by variants affecting the gene represented in this entry.
 == Function ==
-[https://www.uniprot.org/uniprot/S12A3_HUMAN S12A3_HUMAN] Electroneutral sodium and chloride ion cotransporter. In kidney distal convoluted tubules, key mediator of sodium and chloride reabsorption (PubMed:21613606, PubMed:22009145). Receptor for the pro-inflammatory cytokine IL18. Contributes to IL18-induced cytokine production, including IFNG, IL6, IL18 and CCL2. May act either independently of IL18R1, or in a complex with IL18R1 (By similarity).[UniProtKB:P59158]<ref>PMID:21613606</ref> <ref>PMID:22009145</ref>
+[https://www.uniprot.org/uniprot/S12A3_HUMAN S12A3_HUMAN] Electroneutral sodium and chloride ion cotransporter, which acts as a key mediator of sodium and chloride reabsorption in kidney distal convoluted tubules (PubMed:18270262, PubMed:21613606, PubMed:22009145, PubMed:36351028, PubMed:36792826). Also acts as a receptor for the pro-inflammatory cytokine IL18, thereby contributing to IL18-induced cytokine production, including IFNG, IL6, IL18 and CCL2 (By similarity). May act either independently of IL18R1, or in a complex with IL18R1 (By similarity).[UniProtKB:P59158]<ref>PMID:18270262</ref> <ref>PMID:21613606</ref> <ref>PMID:22009145</ref> <ref>PMID:36351028</ref> <ref>PMID:36792826</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 19: / Line 20: @@
 </div>
 <div class="pdbe-citations 7yg1" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Solute carrier family 12 3D structures|Solute carrier family 12 3D structures]]
 == References ==
 <references/>

7yg1

From Proteopedia

Current revision

Cryo-EM structure of the C-terminal domain of the human sodium-chloride cotransporter

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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