7yk7

Cryo-EM structure of the DC591053-bound human relaxin family peptide receptor 4 (RXFP4)-Gi complex

spinqualitylabelsall models 7yk7, resolution 2.75Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7yk7 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 2.75Å Ligands: IYM Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GBG2_BOVIN Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction. 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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