6DG7

Full-length 5-HT3A receptor in a serotonin-bound conformation- State 1

6DG7 の概要

• エントリーDOI: 10.2210/pdb6dg7/pdb
• EMDBエントリー: 7882 7883
• 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, ... (5 entities in total)
• 機能のキーワード: membrane protein
• 由来する生物種: Mus musculus (Mouse)
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 270676.10

構造登録者

Basak, S.,Chakrapani, S. (登録日: 2018-05-17, 公開日: 2018-11-07, 最終更新日: 2024-11-20)

主引用文献

Basak, S.,Gicheru, Y.,Rao, S.,Sansom, M.S.P.,Chakrapani, S.
Cryo-EM reveals two distinct serotonin-bound conformations of full-length 5-HT3Areceptor.
Nature, 563:270-274, 2018

PubMed Abstract: The 5-HT serotonin receptor, a cationic pentameric ligand-gated ion channel (pLGIC), is the clinical target for management of nausea and vomiting associated with radiation and chemotherapies. Upon binding, serotonin induces a global conformational change that encompasses the ligand-binding extracellular domain (ECD), the transmembrane domain (TMD) and the intracellular domain (ICD), the molecular details of which are unclear. Here we present two serotonin-bound structures of the full-length 5-HT receptor in distinct conformations at 3.32 Å and 3.89 Å resolution that reveal the mechanism underlying channel activation. In comparison to the apo 5-HT receptor, serotonin-bound states underwent a large twisting motion in the ECD and TMD, leading to the opening of a 165 Å permeation pathway. Notably, this motion results in the creation of lateral portals for ion permeation at the interface of the TMD and ICD. Combined with molecular dynamics simulations, these structures provide novel insights into conformational coupling across domains and functional modulation.

PubMed: 30401837
DOI: 10.1038/s41586-018-0660-7

実験手法

ELECTRON MICROSCOPY (3.32 Å)