8jef

From Proteopedia

(Difference between revisions)

Current revision

Cryo-EM Structure of the 3HO-HCAR3-Gi complex

Structural highlights

8jef is a 5 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 2.96Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

HCAR3_HUMAN Receptor for 3-OH-octanoid acid mediates a negative feedback regulation of adipocyte lipolysis to counteract prolipolytic influences under conditions of physiological or pathological increases in beta-oxidation rates. Acts as a low affinity receptor for nicotinic acid. This pharmacological effect requires nicotinic acid doses that are much higher than those provided by a normal diet.^[1] ^[2]

Publication Abstract from PubMed

Hydroxycarboxylic acid receptor 3 (HCAR3), a class A G-protein-coupled receptor, is an important cellular energy metabolism sensor with a key role in the regulation of lipolysis in humans. HCAR3 is deeply involved in many physiological processes and serves as a valuable target for the treatment of metabolic diseases, tumors, and immune diseases. Here, we report four cryoelectron microscopy (cryo-EM) structures of human HCAR3-Gi1 complexes with or without agonists: the endogenous ligand 3-hydroxyoctanoic acid, the drug niacin, the highly subtype-specific agonist compound 5c (4-(n-propyl)amino-3-nitrobenzoic acid), and the apo form. Together with mutagenesis and functional analyses, we revealed the recognition mechanisms of HCAR3 for different agonists. In addition, the key residues that determine the ligand selectivity between HCAR2 and HCAR3 were also illuminated. Overall, these findings provide a structural basis for the ligand recognition, activation, and selectivity and G-protein coupling mechanisms of HCAR3, which contribute to the design of HCAR3-targeting drugs with high efficacy and selectivity.

Structural basis for ligand recognition of the human hydroxycarboxylic acid receptor HCAR3.,Ye F, Pan X, Zhang Z, Xiang X, Li X, Zhang B, Ning P, Liu A, Wang Q, Gong K, Li J, Zhu L, Qian C, Chen G, Du Y Cell Rep. 2024 Oct 19;43(11):114895. doi: 10.1016/j.celrep.2024.114895. PMID:39427321^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Wise A, Foord SM, Fraser NJ, Barnes AA, Elshourbagy N, Eilert M, Ignar DM, Murdock PR, Steplewski K, Green A, Brown AJ, Dowell SJ, Szekeres PG, Hassall DG, Marshall FH, Wilson S, Pike NB. Molecular identification of high and low affinity receptors for nicotinic acid. J Biol Chem. 2003 Mar 14;278(11):9869-74. PMID:12522134 doi:10.1074/jbc.M210695200
↑ Ahmed K, Tunaru S, Langhans CD, Hanson J, Michalski CW, Kölker S, Jones PM, Okun JG, Offermanns S. Deorphanization of GPR109B as a receptor for the beta-oxidation intermediate 3-OH-octanoic acid and its role in the regulation of lipolysis. J Biol Chem. 2009 Aug 14;284(33):21928-21933. PMID:19561068 doi:10.1074/jbc.M109.019455
↑ Ye F, Pan X, Zhang Z, Xiang X, Li X, Zhang B, Ning P, Liu A, Wang Q, Gong K, Li J, Zhu L, Qian C, Chen G, Du Y. Structural basis for ligand recognition of the human hydroxycarboxylic acid receptor HCAR3. Cell Rep. 2024 Oct 19;43(11):114895. PMID:39427321 doi:10.1016/j.celrep.2024.114895

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/8jef"

Categories: Homo sapiens | Large Structures | Fang Y | Pan X

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 8jef is ON HOLD
+==Cryo-EM Structure of the 3HO-HCAR3-Gi complex==
+<StructureSection load='8jef' size='340' side='right'caption='[[8jef]], [[Resolution|resolution]] 2.96&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8jef]] 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=8JEF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8JEF 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]] 2.96&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3HO:(3S)-3-HYDROXYOCTANOIC+ACID'>3HO</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=8jef FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8jef OCA], [https://pdbe.org/8jef PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8jef RCSB], [https://www.ebi.ac.uk/pdbsum/8jef PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8jef ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/HCAR3_HUMAN HCAR3_HUMAN] Receptor for 3-OH-octanoid acid mediates a negative feedback regulation of adipocyte lipolysis to counteract prolipolytic influences under conditions of physiological or pathological increases in beta-oxidation rates. Acts as a low affinity receptor for nicotinic acid. This pharmacological effect requires nicotinic acid doses that are much higher than those provided by a normal diet.<ref>PMID:12522134</ref> <ref>PMID:19561068</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Hydroxycarboxylic acid receptor 3 (HCAR3), a class A G-protein-coupled receptor, is an important cellular energy metabolism sensor with a key role in the regulation of lipolysis in humans. HCAR3 is deeply involved in many physiological processes and serves as a valuable target for the treatment of metabolic diseases, tumors, and immune diseases. Here, we report four cryoelectron microscopy (cryo-EM) structures of human HCAR3-Gi1 complexes with or without agonists: the endogenous ligand 3-hydroxyoctanoic acid, the drug niacin, the highly subtype-specific agonist compound 5c (4-(n-propyl)amino-3-nitrobenzoic acid), and the apo form. Together with mutagenesis and functional analyses, we revealed the recognition mechanisms of HCAR3 for different agonists. In addition, the key residues that determine the ligand selectivity between HCAR2 and HCAR3 were also illuminated. Overall, these findings provide a structural basis for the ligand recognition, activation, and selectivity and G-protein coupling mechanisms of HCAR3, which contribute to the design of HCAR3-targeting drugs with high efficacy and selectivity.
-Authors: Fang, Y., Pan, X.
+Structural basis for ligand recognition of the human hydroxycarboxylic acid receptor HCAR3.,Ye F, Pan X, Zhang Z, Xiang X, Li X, Zhang B, Ning P, Liu A, Wang Q, Gong K, Li J, Zhu L, Qian C, Chen G, Du Y Cell Rep. 2024 Oct 19;43(11):114895. doi: 10.1016/j.celrep.2024.114895. PMID:39427321<ref>PMID:39427321</ref>
-Description: Cryo-EM Structure of the 3HO-HCAR3-Gi complex
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Pan, X]]
+<div class="pdbe-citations 8jef" style="background-color:#fffaf0;"></div>
-[[Category: Fang, Y]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Fang Y]]
+[[Category: Pan X]]

8jef

From Proteopedia

Current revision

Cryo-EM Structure of the 3HO-HCAR3-Gi complex

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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