7o7f

Structural basis of the activation of the CC chemokine receptor 5 by a chemokine agonist

spinqualitylabelsall models 7o7f, resolution 3.15Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7o7f is a 7 chain structure with sequence from Bos taurus, 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 3.15Å Ligands: PCA 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 human CC chemokine receptor 5 (CCR5) is a G protein-coupled receptor (GPCR) that plays a major role in inflammation and is involved in cancer, HIV, and COVID-19. Despite its importance as a drug target, the molecular activation mechanism of CCR5, i.e., how chemokine agonists transduce the activation signal through the receptor, is yet unknown. Here, we report the cryo-EM structure of wild-type CCR5 in an active conformation bound to the chemokine super-agonist [6P4]CCL5 and the heterotrimeric G(i) protein. The structure provides the rationale for the sequence-activity relation of agonist and antagonist chemokines. The N terminus of agonist chemokines pushes onto specific structural motifs at the bottom of the orthosteric pocket that activate the canonical GPCR microswitch network. This activation mechanism differs substantially from other CC chemokine receptors that bind chemokines with shorter N termini in a shallow binding mode involving unique sequence signatures and a specialized activation mechanism. Structural basis of the activation of the CC chemokine receptor 5 by a chemokine agonist.,Isaikina P, Tsai CJ, Dietz N, Pamula F, Grahl A, Goldie KN, Guixa-Gonzalez R, Branco C, Paolini-Bertrand M, Calo N, Cerini F, Schertler GFX, Hartley O, Stahlberg H, Maier T, Deupi X, Grzesiek S Sci Adv. 2021 Jun 16;7(25):eabg8685. doi: 10.1126/sciadv.abg8685. Print 2021 Jun. PMID:34134983 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Transducin 3D structures

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