8ihj

Cryo-EM structure of HCA3-Gi complex with acifran

spinqualitylabelsall models 8ihj, resolution 3.07Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8ihj is a 5 chain structure with sequence from Escherichia coli, Homo sapiens, Mus musculus and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.07Å Ligands: P9X Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Hydroxycarboxylic acid receptors (HCA) are expressed in various tissues and immune cells. HCA2 and its agonist are thus important targets for treating inflammatory and metabolic disorders. Only limited information is available, however, on the active-state binding of HCAs with agonists. Here, we present cryo-EM structures of human HCA2-Gi and HCA3-Gi signaling complexes binding with multiple compounds bound. Agonists were revealed to form a salt bridge with arginine, which is conserved in the HCA family, to activate these receptors. Extracellular regions of the receptors form a lid-like structure that covers the ligand-binding pocket. Although transmembrane (TM) 6 in HCAs undergoes dynamic conformational changes, ligands do not directly interact with amino acids in TM6, suggesting that indirect signaling induces a slight shift in TM6 to activate Gi proteins. Structural analyses of agonist-bound HCA2 and HCA3 together with mutagenesis and molecular dynamics simulation provide molecular insights into HCA ligand recognition and activation mechanisms. Structural basis of hydroxycarboxylic acid receptor signaling mechanisms through ligand binding.,Suzuki S, Tanaka K, Nishikawa K, Suzuki H, Oshima A, Fujiyoshi Y Nat Commun. 2023 Sep 22;14(1):5899. doi: 10.1038/s41467-023-41650-7. PMID:37736747 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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