6drz

Structural Determinants of Activation and Biased Agonism at the 5-HT2B Receptor

spinqualitylabelsall models 6drz, resolution 3.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6drz is a 1 chain structure with sequence from Escherichia coli and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.102Å Ligands: CLR, H8J, OLA, OLC, PEG, PO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function C562_ECOLX Electron-transport protein of unknown function.5HT2B_HUMAN This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Plays a role in the regulation of impulsive behavior. Publication Abstract from PubMed Serotonin (5-hydroxytryptamine; 5-HT) receptors modulate a variety of physiological processes ranging from perception, cognition and emotion to vascular and smooth muscle contraction, platelet aggregation, gastrointestinal function and reproduction. Drugs that interact with 5-HT receptors effectively treat diseases as diverse as migraine headaches, depression and obesity. Here we present four structures of a prototypical serotonin receptor-the human 5-HT2B receptor-in complex with chemically and pharmacologically diverse drugs, including methysergide, methylergonovine, lisuride and LY266097. A detailed analysis of these structures complemented by comprehensive interrogation of signaling illuminated key structural determinants essential for activation. Additional structure-guided mutagenesis experiments revealed binding pocket residues that were essential for agonist-mediated biased signaling and beta-arrestin2 translocation. Given the importance of 5-HT receptors for a large number of therapeutic indications, insights derived from these studies should accelerate the design of safer and more effective medications. Structural determinants of 5-HT2B receptor activation and biased agonism.,McCorvy JD, Wacker D, Wang S, Agegnehu B, Liu J, Lansu K, Tribo AR, Olsen RHJ, Che T, Jin J, Roth BL Nat Struct Mol Biol. 2018 Aug 20. pii: 10.1038/s41594-018-0116-7. doi:, 10.1038/s41594-018-0116-7. PMID:30127358 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also 5-hydroxytryptamine receptor 3D structures

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