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-Structure paper
タイトル | Ca inactivation of the mammalian ryanodine receptor type 1 in a lipidic environment revealed by cryo-EM. |
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ジャーナル・号・ページ | Elife, Vol. 11, Year 2022 |
掲載日 | 2022年3月8日 |
![]() | Ashok R Nayak / Montserrat Samsó / ![]() |
PubMed 要旨 | Activation of the intracellular Ca channel ryanodine receptor (RyR) triggers a cytosolic Ca surge, while elevated cytosolic Ca inhibits the channel in a negative feedback mechanism. Cryogenic ...Activation of the intracellular Ca channel ryanodine receptor (RyR) triggers a cytosolic Ca surge, while elevated cytosolic Ca inhibits the channel in a negative feedback mechanism. Cryogenic electron microscopy of rabbit RyR1 embedded in nanodiscs under partially inactivating Ca conditions revealed an open and a closed-inactivated conformation. Ca binding to the high-affinity site engages the central and C-terminal domains into a block, which pries the S6 four-helix bundle open. Further rotation of this block pushes S6 toward the central axis, closing (inactivating) the channel. Main characteristics of the Ca-inactivated conformation are downward conformation of the cytoplasmic assembly and tightly knit subunit interface contributed by a fully occupied Ca activation site, two inter-subunit resolved lipids, and two salt bridges between the EF hand domain and the S2-S3 loop validated by disease-causing mutations. The structural insight illustrates the prior Ca activation prerequisite for Ca inactivation and provides for a seamless transition from inactivated to closed conformations. |
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手法 | EM (単粒子) |
解像度 | 3.3 - 4.3 Å |
構造データ | ![]() EMDB-22597: EMDB-22616, PDB-7k0t: EMDB-25828, PDB-7tdg: EMDB-25829, PDB-7tdh: EMDB-25830, PDB-7tdi: EMDB-25831, PDB-7tdj: EMDB-25832, PDB-7tdk: ![]() EMDB-25833: |
化合物 | ![]() ChemComp-ACP: ![]() ChemComp-ZN: ![]() ChemComp-CA: ![]() ChemComp-POV: ![]() ChemComp-HOH: |
由来 |
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![]() | TRANSPORT PROTEIN / Ryanodine Receptor / RyR1 / Intracellular Calcium channel / Excitation-Contraction coupling / ATP / Ca2+ / Inactivation |