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

Rebecca J. Moen, Sinziana Cornea, Daniel E. Oseid, Benjamin P. Binder, Jennifer C. Klein, David D. Thomas

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)345-349
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume453
Issue number3
DOIs
StatePublished - Oct 24 2014

Keywords

  • Dictyostelium
  • Glutathionylation
  • Methionine
  • Methionine sulfoxide reductase (Msr)
  • Myosin II
  • Reactive oxygen species (ROS)

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