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-Structure paper
タイトル | Conformational motions and ligand-binding underlying gating and regulation in IPR channel. |
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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 | EMDB-27982, PDB-8eaq: EMDB-27983, PDB-8ear: |
化合物 | ChemComp-ZN: ChemComp-CA: ChemComp-PLX: ChemComp-ATP: ChemComp-I3P: |
由来 |
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キーワード | MEMBRANE PROTEIN / Calcium channel / lipid nanodisc |