Redox-sensitive residue in the actin-binding interface of myosin

We have examined the chemical and functional reversibility of oxidative modification in myosin. Redox regulation has emerged as a crucial modulator of protein function, with particular relevance to aging. We previously identified a single methionine residue in Dictyostelium discoideum (Dicty) myosin...

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Published in:Biochemical and biophysical research communications 2014-10, Vol.453 (3), p.345-349
Main Authors: Moen, Rebecca J, Cornea, Sinziana, Oseid, Daniel E, Binder, Benjamin P, Klein, Jennifer C, Thomas, David D
Format: Article
Language:English
Subjects:
Actins - metabolism
Amino Acid Sequence
Binding Sites
Catalytic Domain
Glutathione - metabolism
Humans
Molecular Sequence Data
Mutagenesis, Site-Directed
Myosins - chemistry
Myosins - genetics
Myosins - metabolism
Oxidation-Reduction
Sequence Homology, Amino Acid
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Summary:We have examined the chemical and functional reversibility of oxidative modification in myosin. Redox regulation has emerged as a crucial modulator of protein function, with particular relevance to aging. We previously identified a single methionine residue in Dictyostelium discoideum (Dicty) myosin II (M394, near the myosin cardiomyopathy loop in the actin-binding interface) that is functionally sensitive to oxidation. We now show that oxidation of M394 is reversible by methionine sulfoxide reductase (Msr), restoring actin-activated ATPase activity. Sequence alignment reveals that M394 of Dicty myosin II is a cysteine residue in all human isoforms of skeletal and cardiac myosin. Using Dicty myosin II as a model for site-specific redox sensitivity of this Cys residue, the M394C mutant can be glutathionylated in vitro, resulting in reversible inhibition of actin-activated ATPase activity, with effects similar to those of methionine oxidation at this site. This work illustrates the potential for myosin to function as a redox sensor in both non-muscle and muscle cells, modulating motility/contractility in response to oxidative stress.
ISSN:0006-291X
1090-2104
1090-2104
DOI:10.1016/j.bbrc.2014.09.072