The C-terminal 100 amino acids of the RyR (ryanodine receptor), referred to as the C-terminal tail, is a highly conserved sequence that is present in all known RyR isoforms and which has been implicated in channel function. Deleting the final 15 amino acids from the full-length skeletal muscle RyR resulted in an inactive channel, attributed to impaired assembly of a tetrameric RyR complex [Gao, Tripathy, Lu and Meissner (1997) FEBS Lett. 412, 223–226]. To account for these observations, the C-terminal tail itself may be an important molecular determinant of oligomerization. Alternatively, the large N-terminal cytoplasmic domain may fold back upon itself to interact with the C-terminal tail to provide a correctly folded tetrameric structure. We explored these possibilities for RyR2 (cardiac RyR) using the yeast two-hybrid interaction assay and in vitro translation followed by immunoprecipitation and chemical cross-linking. The data indicate that the C-terminal tail of RyR2 is capable of self-tetramerization. Moreover, a truncated C-terminal tail, lacking the final 15 amino acids, failed to self-associate. These observations suggest that the intrinsic ability of the RyR C-terminal tail to self-tetramerize may be vitally important for the oligomeric assembly of the native RyR channel.
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December 2003
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Research Article|
December 15 2003
Oligomerization of the cardiac ryanodine receptor C-terminal tail
Richard STEWART;
Richard STEWART
Wales Heart Research Institute, Department of Cardiology, University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, U.K.
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Spyros ZISSIMOPOULOS;
Spyros ZISSIMOPOULOS
Wales Heart Research Institute, Department of Cardiology, University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, U.K.
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F. Anthony LAI
F. Anthony LAI
1
Wales Heart Research Institute, Department of Cardiology, University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, U.K.
1To whom correspondence should be addressed (e-mail LaiT@cardiff.ac.uk).
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Publisher: Portland Press Ltd
Received:
April 22 2003
Revision Received:
August 22 2003
Accepted:
September 08 2003
Accepted Manuscript online:
September 08 2003
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2003
2003
Biochem J (2003) 376 (3): 795–799.
Article history
Received:
April 22 2003
Revision Received:
August 22 2003
Accepted:
September 08 2003
Accepted Manuscript online:
September 08 2003
Citation
Richard STEWART, Spyros ZISSIMOPOULOS, F. Anthony LAI; Oligomerization of the cardiac ryanodine receptor C-terminal tail. Biochem J 15 December 2003; 376 (3): 795–799. doi: https://doi.org/10.1042/bj20030597
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