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

doi:10.1016/j.bbrc.2014.09.072

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 journal › Article › peer-review

21 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 language	English (US)
Pages (from-to)	345-349
Number of pages	5
Journal	Biochemical and Biophysical Research Communications
Volume	453
Issue number	3
DOIs	https://doi.org/10.1016/j.bbrc.2014.09.072
State	Published - Oct 24 2014

Bibliographical note

Funding Information:
We thank Margaret Titus for expert consultation regarding Dicty myosin. We thank Ivan Rayment for the S1dC plasmid. This work was supported by NIH grants to DDT ( R37 AG026160 ) and RJM ( F31 AG037303 ) and from AHA to DEO ( 12UFEL12040063 ). We received excellent assistance with mass spectrometry from Bruce Witthuhn at the Center for Mass Spectrometry and Proteomics at the University of Minnesota. The Biophysical Spectroscopy Center and Biomedical Genomics Center at the University of Minnesota were essential for this work.

Publisher Copyright:
© 2014 Elsevier Inc.

Keywords

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

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10.1016/j.bbrc.2014.09.072

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title = "Redox-sensitive residue in the actin-binding interface of myosin",

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.",

keywords = "Dictyostelium, Glutathionylation, Methionine, Methionine sulfoxide reductase (Msr), Myosin II, Reactive oxygen species (ROS)",

author = "Moen, \{Rebecca J.\} and Sinziana Cornea and Oseid, \{Daniel E.\} and Binder, \{Benjamin P.\} and Klein, \{Jennifer C.\} and Thomas, \{David D.\}",

note = "Funding Information: We thank Margaret Titus for expert consultation regarding Dicty myosin. We thank Ivan Rayment for the S1dC plasmid. This work was supported by NIH grants to DDT ( R37 AG026160 ) and RJM ( F31 AG037303 ) and from AHA to DEO ( 12UFEL12040063 ). We received excellent assistance with mass spectrometry from Bruce Witthuhn at the Center for Mass Spectrometry and Proteomics at the University of Minnesota. The Biophysical Spectroscopy Center and Biomedical Genomics Center at the University of Minnesota were essential for this work. Publisher Copyright: {\textcopyright} 2014 Elsevier Inc.",

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AU - Moen, Rebecca J.

AU - Cornea, Sinziana

AU - Oseid, Daniel E.

AU - Binder, Benjamin P.

AU - Klein, Jennifer C.

AU - Thomas, David D.

N1 - Funding Information: We thank Margaret Titus for expert consultation regarding Dicty myosin. We thank Ivan Rayment for the S1dC plasmid. This work was supported by NIH grants to DDT ( R37 AG026160 ) and RJM ( F31 AG037303 ) and from AHA to DEO ( 12UFEL12040063 ). We received excellent assistance with mass spectrometry from Bruce Witthuhn at the Center for Mass Spectrometry and Proteomics at the University of Minnesota. The Biophysical Spectroscopy Center and Biomedical Genomics Center at the University of Minnesota were essential for this work. Publisher Copyright: © 2014 Elsevier Inc.

PY - 2014/10/24

Y1 - 2014/10/24

N2 - 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.

AB - 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.

KW - Dictyostelium

KW - Glutathionylation

KW - Methionine

KW - Methionine sulfoxide reductase (Msr)

KW - Myosin II

KW - Reactive oxygen species (ROS)

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DO - 10.1016/j.bbrc.2014.09.072

M3 - Article

C2 - 25264102

AN - SCOPUS:84918838475

SN - 0006-291X

VL - 453

SP - 345

EP - 349

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 3

ER -

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

Abstract

Bibliographical note

Keywords

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