6his | pdb_00006his

Mouse serotonin 5-HT3 receptor, tropisetron-bound, T conformation

spinqualitylabelsall models 6his, resolution 4.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6his is a 5 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: BMA, NAG, TKT Gene: Htr3a, 5ht3, Htr3 (LK3 transgenic mice) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [5HT3A_MOUSE] 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 is a ligand-gated ion channel, which when activated causes fast, depolarizing responses in neurons. It is a cation-specific, but otherwise relatively nonselective, ion channel. Publication Abstract from PubMed The serotonin 5-HT3 receptor is a pentameric ligand-gated ion channel (pLGIC). It belongs to a large family of receptors that function as allosteric signal transducers across the plasma membrane(1,2); upon binding of neurotransmitter molecules to extracellular sites, the receptors undergo complex conformational transitions that result in transient opening of a pore permeable to ions. 5-HT3 receptors are therapeutic targets for emesis and nausea, irritable bowel syndrome and depression(3). In spite of several reported pLGIC structures(4-8), no clear unifying view has emerged on the conformational transitions involved in channel gating. Here we report four cryo-electron microscopy structures of the full-length mouse 5-HT3 receptor in complex with the anti-emetic drug tropisetron, with serotonin, and with serotonin and a positive allosteric modulator, at resolutions ranging from 3.2 A to 4.5 A. The tropisetron-bound structure resembles those obtained with an inhibitory nanobody(5) or without ligand(9). The other structures include an 'open' state and two ligand-bound states. We present computational insights into the dynamics of the structures, their pore hydration and free-energy profiles, and characterize movements at the gate level and cation accessibility in the pore. Together, these data deepen our understanding of the gating mechanism of pLGICs and capture ligand binding in unprecedented detail. Conformational transitions of the serotonin 5-HT3 receptor.,Polovinkin L, Hassaine G, Perot J, Neumann E, Jensen AA, Lefebvre SN, Corringer PJ, Neyton J, Chipot C, Dehez F, Schoehn G, Nury H Nature. 2018 Nov;563(7730):275-279. doi: 10.1038/s41586-018-0672-3. Epub 2018 Oct, 31. PMID:30401839 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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