Malignant hyperthermia mutation sites in the Leu(2442)-Pro(2477) (DP4) region of RyR1 (ryanodine receptor 1) are clustered in a structurally and functionally definable area
To explain the mechanism of pathogenesis of channel disorder in MH (malignant hyperthermia), we have proposed a model in which tight interactions between the N-terminal and central domains of RyR1 (ryanodine receptor 1) stabilize the closed state of the channel, but mutation in these domains weakens the interdomain interaction and destabilizes the channel. DP4 (domain peptide 4), a peptide corresponding to residues Leu2442-Pro2477 of the central domain, also weakens the domain interaction and...[Show more]
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