8yuv

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

spinqualitylabelsall models 8yuv, resolution 3.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8yuv 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 3Å Ligands: A1LY4, CLR Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function 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. 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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