8hj0: Difference between revisions

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-'''Unreleased structure'''
-The entry 8hj0 is ON HOLD  until Paper Publication
+==GPR21(m5) and G15 complex==
+<StructureSection load='8hj0' size='340' side='right'caption='[[8hj0]], [[Resolution|resolution]] 3.12&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8hj0]] is a 5 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=8HJ0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8HJ0 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=8hj0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8hj0 OCA], [https://pdbe.org/8hj0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8hj0 RCSB], [https://www.ebi.ac.uk/pdbsum/8hj0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8hj0 ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/GNAS2_HUMAN GNAS2_HUMAN] Pseudopseudohypoparathyroidism;Pseudohypoparathyroidism type 1A;Progressive osseous heteroplasia;Polyostotic fibrous dysplasia;Monostotic fibrous dysplasia;Pseudohypoparathyroidism type 1C;Pseudohypoparathyroidism type 1B;McCune-Albright syndrome. The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry. Most affected individuals have defects in methylation of the gene. In some cases microdeletions involving the STX16 appear to cause loss of methylation at exon A/B of GNAS, resulting in PHP1B. Paternal uniparental isodisomy have also been observed.  The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.
+== Function ==
+[https://www.uniprot.org/uniprot/GNAS2_HUMAN GNAS2_HUMAN] Guanine nucleotide-binding proteins (G proteins) function as transducers in numerous signaling pathways controlled by G protein-coupled receptors (GPCRs) (PubMed:17110384). Signaling involves the activation of adenylyl cyclases, resulting in increased levels of the signaling molecule cAMP (PubMed:26206488, PubMed:8702665). GNAS functions downstream of several GPCRs, including beta-adrenergic receptors (PubMed:21488135). Stimulates the Ras signaling pathway via RAPGEF2 (PubMed:12391161).<ref>PMID:12391161</ref> <ref>PMID:17110384</ref> <ref>PMID:21488135</ref> <ref>PMID:26206488</ref> <ref>PMID:8702665</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+GPR21 is a class-A orphan G protein-coupled receptor (GPCR) and a potential therapeutic target for type 2 diabetes and other metabolic disorders. This receptor shows high basal activity in coupling to multiple G proteins in the absence of any known endogenous agonist or synthetic ligand. Here, we present the structures of ligand-free human GPR21 bound to heterotrimeric miniGs and miniG15 proteins, respectively. We identified an agonist-like motif in extracellular loop 2 (ECL2) that occupies the orthosteric pocket and promotes receptor activation. A side pocket that may be employed as a new ligand binding site was also uncovered. Remarkably, G protein binding is accommodated by a flexible cytoplasmic portion of transmembrane helix 6 (TM6) which adopts little or undetectable outward movement. These findings will enable the design of modulators for GPR21 for understanding its signal transduction and exploring opportunity for deorphanization.
-Authors: Chen, B., Lin, X.
+Cryo-EM structures of orphan GPR21 signaling complexes.,Lin X, Chen B, Wu Y, Han Y, Qi A, Wang J, Yang Z, Wei X, Zhao T, Wu L, Xie X, Sun J, Zheng J, Zhao S, Xu F Nat Commun. 2023 Jan 13;14(1):216. doi: 10.1038/s41467-023-35882-w. PMID:36639690<ref>PMID:36639690</ref>
-Description: GPR21(m5) and G15 complex
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Chen, B]]
+<div class="pdbe-citations 8hj0" style="background-color:#fffaf0;"></div>
-[[Category: Lin, X]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Chen B]]
+[[Category: Lin X]]