Association of a mutation in the ryanodine receptor 1 gene with equine malignant hyperthermia

2004 ◽  
Vol 30 (3) ◽  
pp. 356-365 ◽  
Author(s):  
Monica Aleman ◽  
Joyce Riehl ◽  
Brian M. Aldridge ◽  
Richard A. Lecouteur ◽  
Jeffrey L. Stott ◽  
...  
Keyword(s):  
Malignant Hyperthermia ◽  
Ryanodine Receptor ◽  
Ryanodine Receptor 1

scholarly journals Malignant hyperthermia mutation sites in the Leu2442–Pro2477 (DP4) region of RyR1 (ryanodine receptor 1) are clustered in a structurally and functionally definable area

2006 ◽  
Vol 401 (1) ◽  
pp. 333-339 ◽  
Author(s):  
Mark L. Bannister ◽  
Tomoyo Hamada ◽  
Takashi Murayama ◽  
Peta J. Harvey ◽  
Marco G. Casarotto ◽  
...  
Keyword(s):  
Malignant Hyperthermia ◽  
Ryanodine Receptor ◽  
Structural Studies ◽  
Amino Acid Residues ◽  
Domain Interaction ◽  
Closed State ◽  
Interdomain Interaction ◽  
Ryanodine Receptor 1 ◽  
Domain Peptide ◽  
Interdomain Interactions

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 produces MH-like channel destabilization, whereas an MH mutation (R2458C) in DP4 abolishes these effects. Thus DP4 and its mutants serve as excellent tools for structure–function studies. Other MH mutations have been reported in the literature involving three other amino acid residues in the DP4 region (Arg2452, Ile2453 and Arg2454). In the present paper we investigated the activity of several mutants of DP4 at these three residues. The ability to activate ryanodine binding or to effect Ca2+ release was severely diminished for each of the MH mutants. Other substitutions were less effective. Structural studies, using NMR analysis, revealed that the peptide has two α-helical regions. It is apparent that the MH mutations are clustered at the C-terminal end of the first helix. The data in the present paper indicates that mutation of residues in this region disrupts the interdomain interactions that stabilize the closed state of the channel.

scholarly journals Functional Characterization of C-terminal Ryanodine Receptor 1 Variants Associated with Central Core Disease or Malignant Hyperthermia

2017 ◽  
Vol 4 (2) ◽  
pp. 147-158 ◽  
Author(s):  
Remai Parker ◽  
Anja H. Schiemann ◽  
Elaine Langton ◽  
Terasa Bulger ◽  
Neil Pollock ◽  
...  
Keyword(s):  
Malignant Hyperthermia ◽  
Ryanodine Receptor ◽  
Functional Characterization ◽  
Central Core ◽  
Central Core Disease ◽  
Ryanodine Receptor 1

3,5-Di-t-butyl catechol is a potent human ryanodine receptor 1 activator, not suitable for the diagnosis of malignant hyperthermia susceptibility

2012 ◽  
Vol 66 (1) ◽  
pp. 80-87
Author(s):  
Caterina Lacava ◽  
Andrea Michalek-Sauberer ◽  
Birgit Kraft ◽  
Giampietro Sgaragli ◽  
Elisabeth Sipos ◽  
...  
Keyword(s):  
Malignant Hyperthermia ◽  
Ryanodine Receptor ◽  
Malignant Hyperthermia Susceptibility ◽  
Ryanodine Receptor 1

Novel Double and Single Ryanodine Receptor 1 Variants in Two Austrian Malignant Hyperthermia Families

2012 ◽  
Vol 114 (5) ◽  
pp. 1017-1025 ◽  
Author(s):  
Alexius Kaufmann ◽  
Birgit Kraft ◽  
Andrea Michalek-Sauberer ◽  
Marta Weindlmayr ◽  
Hans G. Kress ◽  
...  
Keyword(s):  
Malignant Hyperthermia ◽  
Ryanodine Receptor ◽  
Ryanodine Receptor 1
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