6MU2

Structure of full-length IP3R1 channel in the Apo-state

6MU2 の概要

• エントリーDOI: 10.2210/pdb6mu2/pdb
• EMDBエントリー: 9243 9244
• 分子名称: Inositol 1,4,5-trisphosphate receptor type 1 (1 entity in total)
• 機能のキーワード: inositol 1, 4, 5-trisphosphate receptor, calcium release channel, neuronal type 1, membrane protein
• 由来する生物種: Rattus norvegicus (Rat)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 1254629.62

構造登録者

Serysheva, I.I.,Fan, G.,Baker, M.R.,Wang, Z.,Seryshev, A.,Ludtke, S.J.,Baker, M.L. (登録日: 2018-10-22, 公開日: 2018-12-05, 最終更新日: 2024-10-30)

主引用文献

Fan, G.,Baker, M.R.,Wang, Z.,Seryshev, A.B.,Ludtke, S.J.,Baker, M.L.,Serysheva, I.I.
Cryo-EM reveals ligand induced allostery underlying InsP3R channel gating.
Cell Res., 28:1158-1170, 2018

PubMed Abstract: Inositol-1,4,5-trisphosphate receptors (InsPRs) are cation channels that mobilize Ca from intracellular stores in response to a wide range of cellular stimuli. The paradigm of InsPR activation is the coupled interplay between binding of InsP and Ca that switches the ion conduction pathway between closed and open states to enable the passage of Ca through the channel. However, the molecular mechanism of how the receptor senses and decodes ligand-binding signals into gating motion remains unknown. Here, we present the electron cryo-microscopy structure of InsPR1 from rat cerebellum determined to 4.1 Å resolution in the presence of activating concentrations of Ca and adenophostin A (AdA), a structural mimetic of InsP and the most potent known agonist of the channel. Comparison with the 3.9 Å-resolution structure of InsPR1 in the Apo-state, also reported herein, reveals the binding arrangement of AdA in the tetrameric channel assembly and striking ligand-induced conformational rearrangements within cytoplasmic domains coupled to the dilation of a hydrophobic constriction at the gate. Together, our results provide critical insights into the mechanistic principles by which ligand-binding allosterically gates InsPR channel.

PubMed: 30470765
DOI: 10.1038/s41422-018-0108-5

実験手法

ELECTRON MICROSCOPY (3.9 Å)