8hpt

Structure of C5a-pep bound mouse C5aR1 in complex with Go

spinqualitylabelsall models 8hpt, resolution 3.39Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8hpt is a 6 chain structure with sequence from Homo sapiens, Mus musculus and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.39Å Ligands: ALC, DAR, MEA, ZAL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function C5AR1_MOUSE Receptor for the chemotactic and inflammatory peptide anaphylatoxin C5a. The ligand interacts with at least two sites on the receptor: a high-affinity site on the extracellular N-terminus, and a second site in the transmembrane region which activates downstream signaling events. Receptor activation stimulates chemotaxis, granule enzyme release, intracellular calcium release and superoxide anion production.[UniProtKB:P21730] Publication Abstract from PubMed The complement system is a critical part of our innate immune response, and the terminal products of this cascade, anaphylatoxins C3a and C5a, exert their physiological and pathophysiological responses primarily via two GPCRs, C3aR and C5aR1. However, the molecular mechanism of ligand recognition, activation, and signaling bias of these receptors remains mostly elusive. Here, we present nine cryo-EM structures of C3aR and C5aR1 activated by their natural and synthetic agonists, which reveal distinct binding pocket topologies of complement anaphylatoxins and provide key insights into receptor activation and transducer coupling. We also uncover the structural basis of a naturally occurring mechanism to dampen the inflammatory response of C5a via proteolytic cleavage of the terminal arginine and the G-protein signaling bias elicited by a peptide agonist of C3aR identified here. In summary, our study elucidates the innerworkings of the complement anaphylatoxin receptors and should facilitate structure-guided drug discovery to target these receptors in a spectrum of disorders. Molecular basis of anaphylatoxin binding, activation, and signaling bias at complement receptors.,Yadav MK, Maharana J, Yadav R, Saha S, Sarma P, Soni C, Singh V, Saha S, Ganguly M, Li XX, Mohapatra S, Mishra S, Khant HA, Chami M, Woodruff TM, Banerjee R, Shukla AK, Gati C Cell. 2023 Oct 26;186(22):4956-4973.e21. doi: 10.1016/j.cell.2023.09.020. Epub , 2023 Oct 17. PMID:37852260 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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