7s8m

CryoEM structure of Gi-coupled MRGPRX2 with peptide agonist Cortistatin-14CryoEM structure of Gi-coupled MRGPRX2 with peptide agonist Cortistatin-14

Structural highlights 7s8m is a 6 chain structure with sequence from Escherichia coli, 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 2.54Å 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 The MRGPRX family of receptors (MRGPRX1-4) is a family of mas-related G-protein-coupled receptors that have evolved relatively recently(1). Of these, MRGPRX2 and MRGPRX4 are key physiological and pathological mediators of itch and related mast cell-mediated hypersensitivity reactions(2-5). MRGPRX2 couples to both Gi and Gq in mast cells(6). Here we describe agonist-stabilized structures of MRGPRX2 coupled to Gi1 and Gq in ternary complexes with the endogenous peptide cortistatin-14 and with a synthetic agonist probe, respectively, and the development of potent antagonist probes for MRGPRX2. We also describe a specific MRGPRX4 agonist and the structure of this agonist in a complex with MRGPRX4 and Gq. Together, these findings should accelerate the structure-guided discovery of therapeutic agents for pain, itch and mast cell-mediated hypersensitivity. Structure, function and pharmacology of human itch GPCRs.,Cao C, Kang HJ, Singh I, Chen H, Zhang C, Ye W, Hayes BW, Liu J, Gumpper RH, Bender BJ, Slocum ST, Krumm BE, Lansu K, McCorvy JD, Kroeze WK, English JG, DiBerto JF, Olsen RHJ, Huang XP, Zhang S, Liu Y, Kim K, Karpiak J, Jan LY, Abraham SN, Jin J, Shoichet BK, Fay JF, Roth BL Nature. 2021 Dec;600(7887):170-175. doi: 10.1038/s41586-021-04126-6. Epub 2021, Nov 17. PMID:34789874 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Transducin 3D structures

spinqualitylabelsall models 7s8m, resolution 2.54Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image