7dd5
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==Structure of Calcium-Sensing Receptor in complex with NPS-2143== | ==Structure of Calcium-Sensing Receptor in complex with NPS-2143== | ||
| - | <StructureSection load='7dd5' size='340' side='right'caption='[[7dd5]]' scene=''> | + | <StructureSection load='7dd5' size='340' side='right'caption='[[7dd5]], [[Resolution|resolution]] 3.20Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7DD5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7DD5 FirstGlance]. <br> | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7DD5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7DD5 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=7dd5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7dd5 OCA], [https://pdbe.org/7dd5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7dd5 RCSB], [https://www.ebi.ac.uk/pdbsum/7dd5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7dd5 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]] 3.2Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=TRP:TRYPTOPHAN'>TRP</scene>, <scene name='pdbligand=YP1:2-chloro-6-[(2R)-2-hydroxy-3-{[2-methyl-1-(naphthalen-2-yl)propan-2-yl]amino}propoxy]benzonitrile'>YP1</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=7dd5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7dd5 OCA], [https://pdbe.org/7dd5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7dd5 RCSB], [https://www.ebi.ac.uk/pdbsum/7dd5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7dd5 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Calcium-sensing receptor (CaSR) is a class C G protein-coupled receptor (GPCR) that plays an important role in calcium homeostasis and parathyroid hormone secretion. Here, we present multiple cryo-electron microscopy structures of full-length CaSR in distinct ligand-bound states. Ligands (Ca(2+) and l-tryptophan) bind to the extracellular domain of CaSR and induce large-scale conformational changes, leading to the closure of two heptahelical transmembrane domains (7TMDs) for activation. The positive modulator (evocalcet) and the negative allosteric modulator (NPS-2143) occupy the similar binding pocket in 7TMD. The binding of NPS-2143 causes a considerable rearrangement of two 7TMDs, forming an inactivated TM6/TM6 interface. Moreover, a total of 305 disease-causing missense mutations of CaSR have been mapped to the structure in the active state, creating hotspot maps of five clinical endocrine disorders. Our results provide a structural framework for understanding the activation, allosteric modulation mechanism, and disease therapy for class C GPCRs. | ||
| + | |||
| + | Structural basis for activation and allosteric modulation of full-length calcium-sensing receptor.,Wen T, Wang Z, Chen X, Ren Y, Lu X, Xing Y, Lu J, Chang S, Zhang X, Shen Y, Yang X Sci Adv. 2021 Jun 4;7(23). pii: 7/23/eabg1483. doi: 10.1126/sciadv.abg1483. Print, 2021 Jun. PMID:34088669<ref>PMID:34088669</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7dd5" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Current revision
Structure of Calcium-Sensing Receptor in complex with NPS-2143
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