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-Structure paper
タイトル | Structural basis for activation and gating of IP receptors. |
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ジャーナル・号・ページ | Nat Commun, Vol. 13, Issue 1, Page 1408, Year 2022 |
掲載日 | 2022年3月17日 |
著者 | Emily A Schmitz / Hirohide Takahashi / Erkan Karakas / |
PubMed 要旨 | A pivotal component of the calcium (Ca) signaling toolbox in cells is the inositol 1,4,5-triphosphate (IP) receptor (IPR), which mediates Ca release from the endoplasmic reticulum (ER), controlling ...A pivotal component of the calcium (Ca) signaling toolbox in cells is the inositol 1,4,5-triphosphate (IP) receptor (IPR), which mediates Ca release from the endoplasmic reticulum (ER), controlling cytoplasmic and organellar Ca concentrations. IPRs are co-activated by IP and Ca, inhibited by Ca at high concentrations, and potentiated by ATP. However, the underlying molecular mechanisms are unclear. Here we report cryo-electron microscopy (cryo-EM) structures of human type-3 IPR obtained from a single dataset in multiple gating conformations: IP-ATP bound pre-active states with closed channels, IP-ATP-Ca bound active state with an open channel, and IP-ATP-Ca bound inactive state with a closed channel. The structures demonstrate how IP-induced conformational changes prime the receptor for activation by Ca, how Ca binding leads to channel opening, and how ATP modulates the activity, providing insights into the long-sought questions regarding the molecular mechanism underpinning receptor activation and gating. |
リンク | Nat Commun / PubMed:35301323 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.2 - 3.8 Å |
構造データ | EMDB-25667, PDB-7t3p: EMDB-25668, PDB-7t3q: EMDB-25669, PDB-7t3r: EMDB-25670, PDB-7t3t: EMDB-25671, PDB-7t3u: |
化合物 | ChemComp-ZN: ChemComp-I3P: ChemComp-ATP: ChemComp-CA: |
由来 |
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キーワード | METAL TRANSPORT / IP3 receptor / calcium signaling |