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Record 5 of 33
A role for cysteine 3635 of RYR1 in redox modulation and calmodulin binding
External Online Source: doi:10.1074/jbc.274.52.36831
Author and Affiliation:
Porter Moore, C.(Baylor College of Medicine, Department of Molecular Physiology, Houston, Texas 77030, United States)
Zhang, J. Z.
Hamilton, S. L.
Abstract: Oxidation 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.
Publication Date: Dec 24, 1999
Document ID:
20040141738
(Acquired Nov 09, 2004)
Subject Category: LIFE SCIENCES (GENERAL)
Document Type: Journal Article
Publication Information: The Journal of biological chemistry (ISSN 0021-9258); Volume 274; 52; 36831-4
Publisher Information: United States
Contract/Grant/Task Num: AR41729; AR41802
Description: In English
Distribution Limits: Unclassified; Publicly available; Unlimited
Rights: Copyright
NASA Terms: CALMODULIN; CYSTEINE; MODULATION; OXIDATION-REDUCTION REACTIONS; ALKYLATION; AMINO ACIDS; RABBITS
Other Descriptors: CALMODULIN/METABOLISM; RYANODINE RECEPTOR CALCIUM RELEASE CHANNEL/CHEMISTRY/METABOLISM; ALKYLATION; AMINO ACID SEQUENCE; ANIMALS; CYSTEINE; ETHYLMALEIMIDE/METABOLISM; MOLECULAR SEQUENCE DATA; OXIDATION-REDUCTION; RABBITS; STRUCTURE-ACTIVITY RELATIONSHIP; SUPPORT, NON-U.S. GOV'T; SUPPORT, U.S. GOV'T, P.H.S; NASA DISCIPLINE MUSCULOSKELETAL; NASA PROGRAM BIOMEDICAL RESEARCH AND COUNTERMEASURES; NON-NASA CENTER
Availability Source: Other Sources
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