8pm2: Difference between revisions

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-'''Unreleased structure'''
-The entry 8pm2 is ON HOLD  until Paper Publication
+==Structure of the murine trace amine-associated receptor TAAR7f bound to N,N-dimethylcyclohexylamine (DMCH) in complex with mini-Gs trimeric G protein==
+<StructureSection load='8pm2' size='340' side='right'caption='[[8pm2]], [[Resolution|resolution]] 2.92&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8pm2]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Lama_glama Lama glama] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8PM2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8PM2 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]] 2.92&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8IA:~{N},~{N}-dimethylcyclohexanamine'>8IA</scene>, <scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</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=8pm2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8pm2 OCA], [https://pdbe.org/8pm2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8pm2 RCSB], [https://www.ebi.ac.uk/pdbsum/8pm2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8pm2 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 ==
+There are two main families of G protein-coupled receptors that detect odours in humans, the odorant receptors (ORs) and the trace amine-associated receptors (TAARs). Their amino acid sequences are distinct, with the TAARs being most similar to the aminergic receptors such as those activated by adrenaline, serotonin and histamine. To elucidate the structural determinants of ligand recognition by TAARs, we have determined the cryo-EM structure of a murine receptor, mTAAR7f, coupled to the heterotrimeric G protein G(s) and bound to the odorant N,N-dimethylcyclohexylamine (DMCH) to an overall resolution of 2.9 A. DMCH is bound in a hydrophobic orthosteric binding site primarily through van der Waals interactions and a strong charge-charge interaction between the tertiary amine of the ligand and an aspartic acid residue. This site is distinct and non-overlapping with the binding site for the odorant propionate in the odorant receptor OR51E2. The structure, in combination with mutagenesis data and molecular dynamics simulations suggests that the activation of the receptor follows a similar pathway to that of the beta-adrenoceptors, with the significant difference that DMCH interacts directly with one of the main activation microswitch residues.
-Authors: Gusach, A., Lee, Y., Edwards, P.C., Huang, F., Weyand, S.N., Tate, C.G.
+Molecular recognition of an aversive odorant by the murine trace amine-associated receptor TAAR7f.,Gusach A, Lee Y, Khoshgrudi AN, Mukhaleva E, Ma N, Koers EJ, Chen Q, Edwards PC, Huang F, Kim J, Mancia F, Verprintsev DB, Vaidehi N, Weyand SN, Tate CG bioRxiv [Preprint]. 2023 Jul 7:2023.07.07.547762. doi: 10.1101/2023.07.07.547762. PMID:37461561<ref>PMID:37461561</ref>
-Description: Structure of the murine trace amine-associated receptor TAAR7f bound to N,N-dimethylcyclohexylamine (DMCH) in complex with mini-Gs trimeric G protein
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Weyand, S.N]]
+<div class="pdbe-citations 8pm2" style="background-color:#fffaf0;"></div>
-[[Category: Gusach, A]]
+== References ==
-[[Category: Huang, F]]
+<references/>
-[[Category: Edwards, P.C]]
+__TOC__
-[[Category: Lee, Y]]
+</StructureSection>
-[[Category: Tate, C.G]]
+[[Category: Homo sapiens]]
+[[Category: Lama glama]]
+[[Category: Large Structures]]
+[[Category: Mus musculus]]
+[[Category: Edwards PC]]
+[[Category: Gusach A]]
+[[Category: Huang F]]
+[[Category: Lee Y]]
+[[Category: Tate CG]]
+[[Category: Weyand SN]]