7f6g

Cryo-EM structure of human angiotensin receptor AT1R in complex Gq proteins and Sar1-AngII

spinqualitylabelsall models 7f6g, resolution 2.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7f6g is a 5 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 2.9Å Ligands: CLR, NAG, SAR Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The peptide hormone angiotensin II regulates blood pressure mainly through the type 1 angiotensin II receptor AT(1) R and its downstream signaling proteins G(q) and beta-arrestin. AT(1) R blockers, clinically used as antihypertensive drugs, inhibit both signaling pathways, whereas AT(1) R beta-arrestin-biased agonists have shown great potential for the treatment of acute heart failure. Here, we present a cryo-electron microscopy (cryo-EM) structure of the human AT(1) R in complex with a balanced agonist, Sar(1) -AngII, and G(q) protein at 2.9 A resolution. This structure, together with extensive functional assays and computational modeling, reveals the molecular mechanisms for AT(1) R signaling modulation and suggests that a major hydrogen bond network (MHN) inside the receptor serves as a key regulator of AT(1) R signal transduction from the ligand-binding pocket to both G(q) and beta-arrestin pathways. Specifically, we found that the MHN mutations N111(3.35) A and N294(7.45) A induce biased signaling to G(q) and beta-arrestin, respectively. These insights should facilitate AT(1) R structure-based drug discovery for the treatment of cardiovascular diseases. Structural insights into angiotensin receptor signaling modulation by balanced and biased agonists.,Zhang D, Liu Y, Zaidi SA, Xu L, Zhan Y, Chen A, Guo J, Huang XP, Roth BL, Katritch V, Cherezov V, Zhang H EMBO J. 2023 Jun 1;42(11):e112940. doi: 10.15252/embj.2022112940. Epub 2023 Apr , 11. PMID:37038975 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Transducin 3D structures

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