Structural and functional correlates of a mutation in the malignant hyperthermia‐susceptible pig ryanodine receptor

FEBS Letters

Louis, Charles F.²  Litterer, Lynn A.²  Mickelson, Janies R.²  Knudson, C.Michael¹  Yang, Ding-I.³  Campbell, Kevin P.¹  Rempel, William E.⁴  Kennedy, Catharine F.H.² 

[1] Howard Hughes Medical Institute and Department of Physiology and Biophysics, University of Iowa College of Medicine, Iowa City, IA 52242, USA;Department of Veterinary PathoBiology, University of Minnesota, St. Paul, MN 55108, USA;Department of Biochemistry, University of Minnesota, St. Paul, MN 55108, USA;Department of Animal Science, University of Minnesota, St. Paul, MN 55108, USA

关键词: Sarcoplasmic reticulum;    Ryanodine receptor;    Malignant hyperthermia;    Mutation;    Calcium release channel;   

DOI  :  10.1016/0014-5793(92)80208-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The skeletal muscle ryanodine receptor of malignant hyperthermia-susceptible (MHS) pigs contains a mutation at residue 615 that is highly correlated with various abnormalities in the regulation of sarcoplasmic reticulum (SR) Ca²⁺ channel activity. In isolated SR membranes the Arg⁶¹⁵ to Cys⁶¹⁵ ryanodine receptor mutation is now shown to be directly responsible for an altered tryptic peptide map, due to the elimination of the Arg⁶¹⁵ cleavage site. Furthermore, trypsin treatment released 86–99 kDa ryanodine receptor fragments encompassing residue 615 from the SR membranes. We conclude that the 86–99 kDa domain containing residue 615 is near the cytoplasmic surface of the ryanodine receptor and likely near important Ca²⁺ channel regulatory sites.

【 授权许可】

Unknown