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A role for cysteine 3635 of RYR1 in redox modulation and calmodulin bindingOxidation of the skeletal muscle Ca(2+) release channel (RYR1) increases its activity, produces intersubunit disulfide bonds, and blocks its interaction with calmodulin. Conversely, bound calmodulin protects RYR1 from the effects of oxidants (Zhang, J.-Z., Wu, Y., Williams, B. Y., Rodney, G., Mandel, F., Strasburg, G. M., and Hamilton, S. L. (1999) Am. J. Physiol. 276, Cell Physiol. C46-C53). In addition, calmodulin protects RYR1 from trypsin cleavage at amino acids 3630 and 3637 (Moore, C. P., Rodney, G., Zhang, J.-Z., Santacruz-Toloza, L., Strasburg, G. M., and Hamilton, S. L. (1999) Biochemistry 38, 8532-8537). The sequence between these two tryptic sites is AVVACFR. Alkylation of RYR1 with N-ethylmaleimide (NEM) blocks both (35)S-apocalmodulin binding and oxidation-induced intersubunit cross-linking. In the current work, we demonstrate that both cysteines needed for the oxidation-induced intersubunit cross-link are protected from alkylation with N-ethylmaleimide by bound calmodulin. We also show, using N-terminal amino acid sequencing together with analysis of the distribution of [(3)H]NEM labeling with each sequencing cycle, that cysteine 3635 of RYR1 is rapidly labeled by NEM and that this labeling is blocked by bound calmodulin. We propose that cysteine 3635 is located at an intersubunit contact site that is close to or within a calmodulin binding site. These findings suggest that calmodulin and oxidation modulate RYR1 activity by regulating intersubunit interactions in a mutually exclusive manner and that these interactions involve cysteine 3635.
Document ID
20040141738
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
Authors
Porter Moore, C.
(Baylor College of Medicine Houston, Texas 77030, United States)
Zhang, J. Z.
Hamilton, S. L.
Date Acquired
August 22, 2013
Publication Date
December 24, 1999
Publication Information
Publication: The Journal of biological chemistry
Volume: 274
Issue: 52
ISSN: 0021-9258
Subject Category
Life Sciences (General)
Funding Number(s)
CONTRACT_GRANT: AR41802
CONTRACT_GRANT: AR41729
Distribution Limits
Public
Copyright
Other
Keywords
Non-NASA Center
NASA Discipline Musculoskeletal
NASA Program Biomedical Research and Countermeasures

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