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-Structure paper
タイトル | Modulation of cardiac ryanodine receptor 2 by calmodulin. |
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ジャーナル・号・ページ | Nature, Vol. 572, Issue 7769, Page 347-351, Year 2019 |
掲載日 | 2019年7月5日 |
![]() | Deshun Gong / Ximin Chi / Jinhong Wei / Gewei Zhou / Gaoxingyu Huang / Lin Zhang / Ruiwu Wang / Jianlin Lei / S R Wayne Chen / Nieng Yan / ![]() ![]() ![]() |
PubMed 要旨 | The high-conductance intracellular calcium (Ca) channel RyR2 is essential for the coupling of excitation and contraction in cardiac muscle. Among various modulators, calmodulin (CaM) regulates RyR2 ...The high-conductance intracellular calcium (Ca) channel RyR2 is essential for the coupling of excitation and contraction in cardiac muscle. Among various modulators, calmodulin (CaM) regulates RyR2 in a Ca-dependent manner. Here we reveal the regulatory mechanism by which porcine RyR2 is modulated by human CaM through the structural determination of RyR2 under eight conditions. Apo-CaM and Ca-CaM bind to distinct but overlapping sites in an elongated cleft formed by the handle, helical and central domains. The shift in CaM-binding sites on RyR2 is controlled by Ca binding to CaM, rather than to RyR2. Ca-CaM induces rotations and intradomain shifts of individual central domains, resulting in pore closure of the PCB95 and Ca-activated channel. By contrast, the pore of the ATP, caffeine and Ca-activated channel remains open in the presence of Ca-CaM, which suggests that Ca-CaM is one of the many competing modulators of RyR2 gating. |
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手法 | EM (単粒子) |
解像度 | 3.6 - 4.4 Å |
構造データ | |
化合物 | ![]() ChemComp-ZN: ![]() ChemComp-ATP: ![]() ChemComp-CA: ![]() ChemComp-CFF: |
由来 |
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![]() | MEMBRANE PROTEIN / cryo-EM / MEMBRANE PROTEIN/ISOMERASE / MEMBRANE PROTEIN-ISOMERASE complex |