8yuu

Cryo-EM structure of the histamine-bound H3R-Gi complex

spinqualitylabelsall models 8yuu, resolution 2.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8yuu is a 5 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.7Å Ligands: CLR, HSM Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function HRH3_HUMAN The H3 subclass of histamine receptors could mediate the histamine signals in CNS and peripheral nervous system. Signals through the inhibition of adenylate cyclase and displays high constitutive activity (spontaneous activity in the absence of agonist). Agonist stimulation of isoform 3 neither modified adenylate cyclase activity nor induced intracellular calcium mobilization. Publication Abstract from PubMed G-protein-coupled receptors (GPCRs) transmit downstream signals predominantly via G-protein pathways. However, the conformational basis of selective coupling of primary G-protein remains elusive. Histamine receptors H(2)R and H(3)R couple with G(s)- or G(i)-proteins respectively. Here, three cryo-EM structures of H(2)R-G(s) and H(3)R-G(i) complexes are presented at a global resolution of 2.6-2.7 A. These structures reveal the unique binding pose for endogenous histamine in H(3)R, wherein the amino group interacts with E206(5.46) of H(3)R instead of the conserved D114(3.32) of other aminergic receptors. Furthermore, comparative analysis of the H(2)R-G(s) and H(3)R-G(i) complexes reveals that the structural geometry of TM5/TM6 determines the primary G-protein selectivity in histamine receptors. Machine learning (ML)-based structuromic profiling and functional analysis of class A GPCR-G-protein complexes illustrate that TM5 length, TM5 tilt, and TM6 outward movement are key determinants of the G(s) and G(i/o) selectivity among the whole Class A family. Collectively, the findings uncover the common structural geometry within class A GPCRs that determines the primary G(s)- and G(i/o)-coupling selectivity. Molecular Determinant Underlying Selective Coupling of Primary G-Protein by Class A GPCRs.,Shen Q, Tang X, Wen X, Cheng S, Xiao P, Zang SK, Shen DD, Jiang L, Zheng Y, Zhang H, Xu H, Mao C, Zhang M, Hu W, Sun JP, Zhang Y, Chen Z Adv Sci (Weinh). 2024 Apr 22:e2310120. doi: 10.1002/advs.202310120. PMID:38647423 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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