6HIS

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

6HIS の概要

• エントリーDOI: 10.2210/pdb6his/pdb
• EMDBエントリー: 0225 0226 0227 0228
• 分子名称: 5-hydroxytryptamine receptor 3A, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• 機能のキーワード: ion channel, serotonin receptor, pentameric ligand-gated channel, membrane protein
• 由来する生物種: Mus musculus (house mouse)
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 268343.76

構造登録者

Polovinkin, L.,Neumann, E.,Schoehn, G.,Nury, H. (登録日: 2018-08-30, 公開日: 2018-11-07, 最終更新日: 2024-10-09)

主引用文献

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

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: 30401839
DOI: 10.1038/s41586-018-0672-3

実験手法

ELECTRON MICROSCOPY (4.5 Å)