7fig

luteinizing hormone/choriogonadotropin receptor(S277I)-chorionic gonadotropin-Gs complex

spinqualitylabelsall models 7fig, resolution 3.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7fig is a 7 chain structure with sequence from Bos taurus, Homo sapiens, Lama glama and Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.9Å Ligands: NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GBB1_RAT 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 Luteinizing hormone and chorionic gonadotropin are glycoprotein hormones that are related to follicle-stimulating hormone and thyroid-stimulating hormone(1,2). Luteinizing hormone and chorionic gonadotropin are essential to human reproduction and are important therapeutic drugs(3-6). They activate the same G-protein-coupled receptor, luteinizing hormone-choriogonadotropin receptor (LHCGR), by binding to the large extracellular domain(3). Here we report four cryo-electron microscopy structures of LHCGR: two structures of the wild-type receptor in the inactive and active states; and two structures of the constitutively active mutated receptor. The active structures are bound to chorionic gonadotropin and the stimulatory G protein (Gs), and one of the structures also contains Org43553, an allosteric agonist(7). The structures reveal a distinct 'push-and-pull' mechanism of receptor activation, in which the extracellular domain is pushed by the bound hormone and pulled by the extended hinge loop next to the transmembrane domain. A highly conserved 10-residue fragment (P10) from the hinge C-terminal loop at the interface between the extracellular domain and the transmembrane domain functions as a tethered agonist to induce conformational changes in the transmembrane domain and G-protein coupling. Org43553 binds to a pocket of the transmembrane domain and interacts directly with P10, which further stabilizes the active conformation. Together, these structures provide a common model for understanding the signalling of glycoprotein hormone receptors and a basis for drug discovery for endocrine diseases. Structures of full-length glycoprotein hormone receptor signalling complexes.,Duan J, Xu P, Cheng X, Mao C, Croll T, He X, Shi J, Luan X, Yin W, You E, Liu Q, Zhang S, Jiang H, Zhang Y, Jiang Y, Xu HE Nature. 2021 Oct;598(7882):688-692. doi: 10.1038/s41586-021-03924-2. Epub 2021, Sep 22. PMID:34552239 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Transducin 3D structures

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