7yk6

Cryo-EM structure of the compound 4-bound human relaxin family peptide receptor 4 (RXFP4)-Gi complex

spinqualitylabelsall models 7yk6, resolution 3.03Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7yk6 is a 5 chain structure with sequence from Bos taurus, Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.03Å Ligands: IYF Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GNAI2_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. May play a role in cell division. Isoform sGi2: Regulates the cell surface density of dopamine receptors DRD2 by sequestrating them as an intracellular pool. Publication Abstract from PubMed Members of the insulin superfamily regulate pleiotropic biological processes through two types of target-specific but structurally conserved peptides, insulin/insulin-like growth factors and relaxin/insulin-like peptides. The latter bind to the human relaxin family peptide receptors (RXFPs). Here, we report three cryo-electron microscopy structures of RXFP4-G(i) protein complexes in the presence of the endogenous ligand insulin-like peptide 5 (INSL5) or one of the two small molecule agonists, compound 4 and DC591053. The B chain of INSL5 adopts a single alpha-helix that penetrates into the orthosteric pocket, while the A chain sits above the orthosteric pocket, revealing a peptide-binding mode previously unknown. Together with mutagenesis and functional analyses, the key determinants responsible for the peptidomimetic agonism and subtype selectivity were identified. Our findings not only provide insights into ligand recognition and subtype selectivity among class A G protein-coupled receptors, but also expand the knowledge of signaling mechanisms in the insulin superfamily. Ligand recognition mechanism of the human relaxin family peptide receptor 4 (RXFP4).,Chen Y, Zhou Q, Wang J, Xu Y, Wang Y, Yan J, Wang Y, Zhu Q, Zhao F, Li C, Chen CW, Cai X, Bathgate RAD, Shen C, Eric Xu H, Yang D, Liu H, Wang MW Nat Commun. 2023 Jan 30;14(1):492. doi: 10.1038/s41467-023-36182-z. PMID:36717591 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Transducin 3D structures

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