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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 572 347-351 (2019)
Related entries: 6ji0, 6ji8, 6jii, 6jiu, 6jiy, 6jrr, 6jv2

Cited: 59 times
EuropePMC logo PMID: 31278385

Abstract

The high-conductance intracellular calcium (Ca2+) channel RyR2 is essential for the coupling of excitation and contraction in cardiac muscle. Among various modulators, calmodulin (CaM) regulates RyR2 in a Ca2+-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 Ca2+-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 Ca2+ binding to CaM, rather than to RyR2. Ca2+-CaM induces rotations and intradomain shifts of individual central domains, resulting in pore closure of the PCB95 and Ca2+-activated channel. By contrast, the pore of the ATP, caffeine and Ca2+-activated channel remains open in the presence of Ca2+-CaM, which suggests that Ca2+-CaM is one of the many competing modulators of RyR2 gating.

Reviews - 6jrs mentioned but not cited (1)

  1. Regulatory mechanisms of ryanodine receptor/Ca2+ release channel revealed by recent advancements in structural studies. Ogawa H, Kurebayashi N, Yamazawa T, Murayama T. J Muscle Res Cell Motil 42 291-304 (2021)


Reviews citing this publication (16)

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Articles citing this publication (42)

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