7xk2: Difference between revisions
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The | ==Cryo-EM Structure of Human Niacin Receptor HCA2-Gi protein complex== | ||
<StructureSection load='7xk2' size='340' side='right'caption='[[7xk2]], [[Resolution|resolution]] 3.10Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7xk2]] 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=7XK2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7XK2 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]] 3.1Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FI7:2-[[2,2-dimethyl-3-[3-(5-oxidanylpyridin-2-yl)-1,2,4-oxadiazol-5-yl]propanoyl]amino]cyclohexene-1-carboxylic+acid'>FI7</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=7xk2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7xk2 OCA], [https://pdbe.org/7xk2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7xk2 RCSB], [https://www.ebi.ac.uk/pdbsum/7xk2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7xk2 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/HCAR2_HUMAN HCAR2_HUMAN] Acts as a high affinity receptor for both nicotinic acid (also known as niacin) and (D)-beta-hydroxybutyrate and mediates increased adiponectin secretion and decreased lipolysis through G(i)-protein-mediated inhibition of adenylyl cyclase. This pharmacological effect requires nicotinic acid doses that are much higher than those provided by a normal diet. Mediates nicotinic acid-induced apoptosis in mature neutrophils. Receptor activation by nicotinic acid results in reduced cAMP levels which may affect activity of cAMP-dependent protein kinase A and phosphorylation of target proteins, leading to neutrophil apoptosis. The rank order of potency for the displacement of nicotinic acid binding is 5-methyl pyrazole-3-carboxylic acid = pyridine-3-acetic acid > acifran > 5-methyl nicotinic acid = acipimox >> nicotinuric acid = nicotinamide.<ref>PMID:17932499</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The hydroxycarboxylic acid receptor 2 (HCA2) agonist niacin has been used as treatment for dyslipidemia for several decades albeit with skin flushing as a common side-effect in treated individuals. Extensive efforts have been made to identify HCA2 targeting lipid lowering agents with fewer adverse effects, despite little being known about the molecular basis of HCA2 mediated signalling. Here, we report the cryo-electron microscopy structure of the HCA2-G(i) signalling complex with the potent agonist MK-6892, along with crystal structures of HCA2 in inactive state. These structures, together with comprehensive pharmacological analysis, reveal the ligand binding mode and activation and signalling mechanisms of HCA2. This study elucidates the structural determinants essential for HCA2 mediated signalling and provides insights into ligand discovery for HCA2 and related receptors. | |||
Structural insights into the human niacin receptor HCA2-G(i) signalling complex.,Yang Y, Kang HJ, Gao R, Wang J, Han GW, DiBerto JF, Wu L, Tong J, Qu L, Wu Y, Pileski R, Li X, Zhang XC, Zhao S, Kenakin T, Wang Q, Stevens RC, Peng W, Roth BL, Rao Z, Liu ZJ Nat Commun. 2023 Mar 27;14(1):1692. doi: 10.1038/s41467-023-37177-6. PMID:36973264<ref>PMID:36973264</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 7xk2" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Transducin 3D structures|Transducin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: DiBerto JF]] | |||
[[Category: Gao RG]] | |||
[[Category: Han GW]] | |||
[[Category: Kang HJ]] | |||
[[Category: Kenakin T]] | |||
[[Category: Li XM]] | |||
[[Category: Liu ZJ]] | |||
[[Category: Peng W]] | |||
[[Category: Pileski R]] | |||
[[Category: Qu L]] | |||
[[Category: Rao ZH]] | |||
[[Category: Roth BL]] | |||
[[Category: Stevens RC]] | |||
[[Category: Tong JH]] | |||
[[Category: Wang JJ]] | |||
[[Category: Wang Q]] | |||
[[Category: Wu LJ]] | |||
[[Category: Wu YR]] | |||
[[Category: Yang Y]] | |||
[[Category: Zhang XC]] | |||
[[Category: Zhao SW]] | |||