View source for 9kt8


==Cryo-EM structure of HCA2-Gi complex with acifran==
<StructureSection load='9kt8' size='340' side='right'caption='[[9kt8]], [[Resolution|resolution]] 2.73&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9kt8]] 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=9KT8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9KT8 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]] 2.73&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=P9X:(5~{S})-5-methyl-4-oxidanylidene-5-phenyl-furan-2-carboxylic+acid'>P9X</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=9kt8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9kt8 OCA], [https://pdbe.org/9kt8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9kt8 RCSB], [https://www.ebi.ac.uk/pdbsum/9kt8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9kt8 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GNAI1_HUMAN GNAI1_HUMAN] Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(i) proteins are involved in hormonal regulation of adenylate cyclase: they inhibit the cyclase in response to beta-adrenergic stimuli. The inactive GDP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. May play a role in cell division.<ref>PMID:17635935</ref> <ref>PMID:17264214</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Hydroxy-carboxylic acid receptors HCA1, HCA2, and HCA3 can be activated by important intermediates of energy metabolism. Despite the research focusing on HCA2, its clinical application has been limited by adverse effects. Therefore, the role of HCA1 as a promising target for the treatment of lipolysis warrants further exploration. As HCAs exhibit high similarity when activated with diverse selective agonists, a conserved yet unique activation mechanism for HCAs remains undisclosed. Herein, we unveil the cryo-electron microscopy structures of the 3,5-DHBA-HCA1-Gi signaling complex, the acifran- and MK6892-bound HCA2-Gi signaling complexes, and the acifran-HCA3-Gi signaling complex. Comparative analysis across HCAs reveals key residues in HCA1 contributing to the stabilization of the ligand-binding pocket. Furthermore, chimeric complexes and mutational analyses identify residues that are pivotal for HCA2 and HCA3 selectivity. Our findings elucidate critical structural insights into the mechanisms of ligand recognition and activation within HCA1 and broaden our comprehension of ligand specificity binding across the HCA family.

Insights into the Activation Mechanism of HCA1, HCA2, and HCA3.,Wang J, Qian Y, Han Z, Wang Y, Liu Y, Li J, Duanmu Q, Ye S, Qiao A, Wu S J Med Chem. 2025 Feb 27;68(4):4527-4539. doi: 10.1021/acs.jmedchem.4c02567. Epub , 2025 Feb 12. PMID:39936872<ref>PMID:39936872</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9kt8" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Wu S]]