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==Human Calcium-Sensing Receptor bound with L-Trp==
<StructureSection load='7dtu' size='340' side='right'caption='[[7dtu]], [[Resolution|resolution]] 4.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7DTU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7DTU 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]] 4.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=TRP:TRYPTOPHAN'>TRP</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=7dtu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7dtu OCA], [https://pdbe.org/7dtu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7dtu RCSB], [https://www.ebi.ac.uk/pdbsum/7dtu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7dtu ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The human calcium-sensing receptor (CaSR) is a class C G protein-coupled receptor (GPCR) responsible for maintaining Ca(2+) homeostasis in the blood. The general consensus is that extracellular Ca(2+) is the principal agonist of CaSR. Aliphatic and aromatic L-amino acids, such as L-Phe and L-Trp, increase the sensitivity of CaSR towards Ca(2+) and are considered allosteric activators. Crystal structures of the extracellular domain (ECD) of CaSR dimer have demonstrated Ca(2+) and L-Trp binding sites and conformational changes of the ECD upon Ca(2+)/L-Trp binding. However, it remains to be understood at the structural level how Ca(2+)/L-Trp binding to the ECD leads to conformational changes in transmembrane domains (TMDs) and consequent CaSR activation. Here, we determined the structures of full-length human CaSR in the inactive state, Ca(2+)- or L-Trp-bound states, and Ca(2+)/L-Trp-bound active state using single-particle cryo-electron microscopy. Structural studies demonstrate that L-Trp binding induces the closure of the Venus flytrap (VFT) domain of CaSR, bringing the receptor into an intermediate active state. Ca(2+) binding relays the conformational changes from the VFT domains to the TMDs, consequently inducing close contact between the two TMDs of dimeric CaSR, activating the receptor. Importantly, our structural and functional studies reveal that Ca(2+) ions and L-Trp activate CaSR cooperatively. Amino acids are not able to activate CaSR alone, but can promote the receptor activation in the presence of Ca(2+). Our data provide complementary insights into the activation of class C GPCRs and may aid in the development of novel drugs targeting CaSR.

Structural mechanism of cooperative activation of the human calcium-sensing receptor by Ca(2+) ions and L-tryptophan.,Ling S, Shi P, Liu S, Meng X, Zhou Y, Sun W, Chang S, Zhang X, Zhang L, Shi C, Sun D, Liu L, Tian C Cell Res. 2021 Feb 18. pii: 10.1038/s41422-021-00474-0. doi:, 10.1038/s41422-021-00474-0. PMID:33603117<ref>PMID:33603117</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7dtu" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Ling SL]]
[[Category: Liu L]]
[[Category: Liu SL]]
[[Category: Meng XY]]
[[Category: Shi CW]]
[[Category: Shi P]]
[[Category: Sun DM]]
[[Category: Tian CL]]