6HIO
Mouse serotonin 5-HT3 receptor, serotonin-bound, I1 conformation
Summary for 6HIO
| Entry DOI | 10.2210/pdb6hio/pdb |
| EMDB information | 0225 0226 |
| Descriptor | 5-hydroxytryptamine receptor 3A, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total) |
| Functional Keywords | ion channel, serotonin receptor, pentameric ligand-gated channel, membrane protein |
| Biological source | Mus musculus (house mouse) |
| Total number of polymer chains | 5 |
| Total formula weight | 266757.32 |
| Authors | Polovinkin, L.,Neumann, E.,Schoehn, G.,Nury, H. (deposition date: 2018-08-30, release date: 2018-11-07, Last modification date: 2024-11-13) |
| Primary citation | Polovinkin, L.,Hassaine, G.,Perot, J.,Neumann, E.,Jensen, A.A.,Lefebvre, S.N.,Corringer, P.J.,Neyton, J.,Chipot, C.,Dehez, F.,Schoehn, G.,Nury, H. Conformational transitions of the serotonin 5-HT3receptor. Nature, 563:275-279, 2018 Cited by PubMed Abstract: The serotonin 5-HT 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; 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-HT receptors are therapeutic targets for emesis and nausea, irritable bowel syndrome and depression. In spite of several reported pLGIC structures, 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-HT 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 Å to 4.5 Å. The tropisetron-bound structure resembles those obtained with an inhibitory nanobody or without ligand. 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. PubMed: 30401839DOI: 10.1038/s41586-018-0672-3 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (4.2 Å) |
Structure validation
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