6jv2
From Proteopedia
Structure of RyR2 (P/L-Ca2+/Ca2+-CaM dataset)
Structural highlights
Disease[CALM1_HUMAN] The disease is caused by mutations affecting the gene represented in this entry. Mutations in CALM1 are the cause of CPVT4. The disease is caused by mutations affecting the gene represented in this entry. Mutations in CALM1 are the cause of LQT14. Function[CALM1_HUMAN] Calmodulin mediates the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding. Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases and phosphatases. Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis (PubMed:16760425). Mediates calcium-dependent inactivation of CACNA1C (PubMed:26969752). Positively regulates calcium-activated potassium channel activity of KCNN2 (PubMed:27165696).[1] [2] [3] [4] Publication Abstract from PubMedThe high-conductance intracellular calcium (Ca(2+)) channel RyR2 is essential for the coupling of excitation and contraction in cardiac muscle. Among various modulators, calmodulin (CaM) regulates RyR2 in a Ca(2+)-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(2+)-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(2+) binding to CaM, rather than to RyR2. Ca(2+)-CaM induces rotations and intradomain shifts of individual central domains, resulting in pore closure of the PCB95 and Ca(2+)-activated channel. By contrast, the pore of the ATP, caffeine and Ca(2+)-activated channel remains open in the presence of Ca(2+)-CaM, which suggests that Ca(2+)-CaM is one of the many competing modulators of RyR2 gating. Modulation of cardiac ryanodine receptor 2 by calmodulin.,Gong D, Chi X, Wei J, Zhou G, Huang G, Zhang L, Wang R, Lei J, Chen SRW, Yan N Nature. 2019 Jul 5. pii: 10.1038/s41586-019-1377-y. doi:, 10.1038/s41586-019-1377-y. PMID:31278385[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Human | Large Structures | Sus scrofa | Chi, X M | Gong, D S | Huang, G X.Y | Lei, J L | Yan, N | Zhou, G W | Cryo-em | Membrane protein
