8jei

From Proteopedia

Jump to: navigation, search

Cryo-EM Structure of the compuond 5c-HCAR3-Gi complex

Structural highlights

8jei 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 2.73Å
Ligands:CW3
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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[1]

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

Loading citation details..
Citations
reviews cite this structure
No citations found

References

  1. 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

Contents


PDB ID 8jei

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Personal tools