8EAR

Structure of the full-length IP3R1 channel determined in the presence of Calcium/IP3/ATP

8EAR の概要

• エントリーDOI: 10.2210/pdb8ear/pdb
• EMDBエントリー: 27983
• 分子名称: Inositol 1,4,5-trisphosphate receptor type 1, ZINC ION, ADENOSINE-5'-TRIPHOSPHATE, ... (6 entities in total)
• 機能のキーワード: calcium channel, lipid nanodisc, membrane protein
• 由来する生物種: Rattus norvegicus (Norway rat)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 1280721.31

構造登録者

Fan, G.,Baker, M.R.,Terry, L.E.,Arige, V.,Chen, M.,Seryshev, A.B.,Baker, M.L.,Ludtke, S.J.,Yule, D.I.,Serysheva, I.I. (登録日: 2022-08-29, 公開日: 2022-11-23, 最終更新日: 2024-10-23)

主引用文献

Fan, G.,Baker, M.R.,Terry, L.E.,Arige, V.,Chen, M.,Seryshev, A.B.,Baker, M.L.,Ludtke, S.J.,Yule, D.I.,Serysheva, I.I.
Conformational motions and ligand-binding underlying gating and regulation in IP 3 R channel.
Nat Commun, 13:6942-6942, 2022

PubMed Abstract: Inositol-1,4,5-trisphosphate receptors (IPRs) are activated by IP and Ca and their gating is regulated by various intracellular messengers that finely tune the channel activity. Here, using single particle cryo-EM analysis we determined 3D structures of the nanodisc-reconstituted IPR1 channel in two ligand-bound states. These structures provide unprecedented details governing binding of IP, Ca and ATP, revealing conformational changes that couple ligand-binding to channel opening. Using a deep-learning approach and 3D variability analysis we extracted molecular motions of the key protein domains from cryo-EM density data. We find that IP binding relies upon intrinsic flexibility of the ARM2 domain in the tetrameric channel. Our results highlight a key role of dynamic side chains in regulating gating behavior of IPR channels. This work represents a stepping-stone to developing mechanistic understanding of conformational pathways underlying ligand-binding, activation and regulation of the channel.

PubMed: 36376291
DOI: 10.1038/s41467-022-34574-1

実験手法

ELECTRON MICROSCOPY (3.5 Å)