7wu4 | pdb_00007wu4

Cryo-EM structure of the adhesion GPCR ADGRF1 in complex with miniGi

spinqualitylabelsall models 7wu4, resolution 3.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7wu4 is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.4Å Ligands: CLR, K6G Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Adhesion G protein-coupled receptors (aGPCRs) are essential for a variety of physiological processes such as immune responses, organ development, cellular communication, proliferation and homeostasis(1-7). An intrinsic manner of activation that involves a tethered agonist in the N-terminal region of the receptor has been proposed for the aGPCRs(8,9), but its molecular mechanism remains elusive. Here we report the G protein-bound structures of ADGRD1 and ADGRF1, which exhibit many unique features with regard to the tethered agonism. The stalk region that proceeds the first transmembrane helix acts as the tethered agonist by forming extensive interactions with the transmembrane domain; these interactions are mostly conserved in ADGRD1 and ADGRF1, suggesting that a common stalk-transmembrane domain interaction pattern is shared by members of the aGPCR family. A similar stalk binding mode is observed in the structure of autoproteolysis-deficient ADGRF1, supporting a cleavage-independent manner of receptor activation. The stalk-induced activation is facilitated by a cascade of inter-helix interaction cores that are conserved in positions but show sequence variability in these two aGPCRs. Furthermore, the intracellular region of ADGRF1 contains a specific lipid-binding site, which proves to be functionally important and may serve as the recognition site for the previously discovered endogenous ADGRF1 ligand synaptamide. These findings highlight the diversity and complexity of the signal transduction mechanisms of the aGPCRs. Structural basis of tethered agonism of the adhesion GPCRs ADGRD1 and ADGRF1.,Qu X, Qiu N, Wang M, Zhang B, Du J, Zhong Z, Xu W, Chu X, Ma L, Yi C, Han S, Shui W, Zhao Q, Wu B Nature. 2022 Apr;604(7907):779-785. doi: 10.1038/s41586-022-04580-w. Epub 2022 , Apr 13. PMID:35418679 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Transducin 3D structures

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