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Structure paper

タイトル	Conformational motions and ligand-binding underlying gating and regulation in IPR channel.
ジャーナル・号・ページ	Nat Commun, Vol. 13, Issue 1, Page 6942, Year 2022
掲載日	2022年11月14日
著者	Guizhen Fan / Mariah R Baker / Lara E Terry / Vikas Arige / Muyuan Chen / Alexander B Seryshev / Matthew L Baker / Steven J Ludtke / David I Yule / Irina I Serysheva /
PubMed 要旨	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 ...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.
リンク	Nat Commun / PubMed:36376291 / PubMed Central
手法	EM (単粒子)
解像度	3.26 - 3.5 Å
構造データ	27982 8eaq EMDB-27982, PDB-8eaq: Structure of the full-length IP3R1 channel determined at high Ca2+ 手法: EM (単粒子) / 解像度: 3.26 Å 27983 8ear EMDB-27983, PDB-8ear: Structure of the full-length IP3R1 channel determined in the presence of Calcium/IP3/ATP 手法: EM (単粒子) / 解像度: 3.5 Å
化合物	ChemComp-ZN: Unknown entry ChemComp-CA: Unknown entry / カルシウムジカチオン ChemComp-PLX: (9R,11S)-9-({[(1S)-1-HYDROXYHEXADECYL]OXY}METHYL)-2,2-DIMETHYL-5,7,10-TRIOXA-2LAMBDA~5~-AZA-6LAMBDA~5~-PHOSPHAOCTACOSANE-6,6,11-TRIOL / リン脂質YM ChemComp-ATP: ADENOSINE-5'-TRIPHOSPHATE / ATP / ATP, エネルギー貯蔵分子YM / アデノシン三リン酸 ChemComp-I3P: D-MYO-INOSITOL-1,4,5-TRIPHOSPHATE / イノシト-ル1,4,5-トリスりん酸 / イノシトールトリスリン酸
由来	rattus norvegicus (ドブネズミ) Norway rat (ドブネズミ)
キーワード	MEMBRANE PROTEIN (膜タンパク質) / Calcium channel (カルシウムチャネル) / lipid nanodisc