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

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

doi:10.1016/j.bbrc.2014.09.072

Cited by 19 publications

(15 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Is it possible that estradiol acts by influencing other phosphorylation targets involved in myosin-based contractility, such as myosin-binding protein C [28], titin, or troponin [29]? What about other post-translational protein modifications, such as oxidation [12,30]? What are the other components in the estradiol signaling pathway that eventually lead to regulation of SRX [31,32]?…”

Section: Discussionmentioning

confidence: 99%

The myosin super-relaxed state is disrupted by estradiol deficiency

Colson

Petersen

Collins

et al. 2015

Biochemical and Biophysical Research Communications

Self Cite

View full text Add to dashboard Cite

We have used quantitative epifluorescence microscopy of fluorescent ATP to measure single-nucleotide turnover in skinned skeletal muscle fibers from mouse models of female aging and hormone treatment. Aging causes declines in muscle strength, often leading to frailty, disability, and loss of independence for the elderly. Female muscle is additionally affected by age due to reduction of ovarian hormone production with menopause. Estradiol (E2) is the key hormonal signal to skeletal muscle in females, and strength loss is attenuated by E2 treatment. To investigate E2 mechanisms on skeletal muscle, single fibers were isolated from sham-operated or ovariectomized (OVX) mice, with or without E2 treatment, and were incubated with mantATP. We measured decay of mantATP fluorescence in an ATP-chase experiment, as pioneered by Cooke and coworkers, who unveiled a novel regulated state of muscle myosin characterized by slow nucleotide turnover on the order of minutes, termed the super-relaxed state (SRX). We detected a slow phase of nucleotide turnover in approximately one-third of the myosin heads from sham fibers, consistent with SRX. Turnover was substantially faster in OVX fibers, with a turnover time constant for the slow phase of 65 ± 8 s as compared to 102 ± 7 s for sham fibers. 60-day E2 treatment in OVX mice substantially reversed this effect on SRX, while acute exposure of isolated muscles from OVX mice to E2 had no effect. We conclude that E2-mediated signaling reversibly regulates slow ATP turnover by myosin. Age- and hormone-related muscle functional losses may be targetable at the level of myosin structure/function for strategies to offset weakness and metabolic changes that occur with age.

show abstract

Section: Discussionmentioning

confidence: 99%

The myosin super-relaxed state is disrupted by estradiol deficiency

Colson

Petersen

Collins

et al. 2015

Biochemical and Biophysical Research Communications

Self Cite

View full text Add to dashboard Cite

show abstract

“…Both NM- and muscle- myosin II have been proposed to be redox sensors within cells, because both are reversibly oxidized and this oxidation inhibits their interaction with actin and their ATPase activity [96]. This regulatory oxidation occurs at Met394 of protist NM-myosin II [97], which is equivalent to a cysteine that is glutathyolated in mammalian cardiac and skeletal muscle myosin II [96].…”

Section: The Actin Cytoskeleton As a Target Of Oxidantsmentioning

confidence: 99%

“…This regulatory oxidation occurs at Met394 of protist NM-myosin II [97], which is equivalent to a cysteine that is glutathyolated in mammalian cardiac and skeletal muscle myosin II [96]. However, Fiaschi and colleagues [98], who examined myosin oxidation in the context of cell spreading, suggested that only NM-MHC is under redox control.…”

Section: The Actin Cytoskeleton As a Target Of Oxidantsmentioning

confidence: 99%

“…This rounding is important for proper spindle assembly and efficient, error-free chromosome separation [361]. When myosin II is directly oxidized, its activity is inhibited [96]. Therefore, for proper cell division to occur, myosin II must be protected from the elevated levels of ROS during mitosis to enable cell rounding.…”

Section: Redox Regulation Of the Actin Cytoskeleton In Cell Physiologymentioning

confidence: 99%

See 1 more Smart Citation

Redox regulation of the actin cytoskeleton and its role in the vascular system

Huff

Fujii

et al. 2017

Free Radical Biology and Medicine

View full text Add to dashboard Cite

The actin cytoskeleton is critical for form and function of vascular cells, serving mechanical, organizational and signaling roles. Because many cytoskeletal proteins are sensitive to reactive oxygen species, redox regulation has emerged as a pivotal modulator of the actin cytoskeleton and its associated proteins. Here, we summarize work implicating oxidants in altering actin cytoskeletal proteins and focus on how these alterations affect cell migration, proliferation and contraction of vascular cells. Finally, we discuss the role of oxidative modification of the actin cytoskeleton in vivo and highlight its importance for vascular diseases.

show abstract

“…In particular, Met oxidation and subsequent reduction by Met sulfoxide reductase have far-reaching implications in metabolic, cardiovascular, neurological, and immune related dysfunction [10, 11, 12]. We have identified specific Met residues in proteins as targets of oxidation in muscle contractile and regulatory proteins [13, 14, 15]. Met oxidation has been proposed as a mechanism through which the muscle cell responds to oxidative stress by modulating metabolism and energy utilization [16].…”

Section: Introductionmentioning

confidence: 99%

Impact of methionine oxidation on calmodulin structural dynamics

McCarthy

Thompson

Nitu

et al. 2015

Biochemical and Biophysical Research Communications

Self Cite

View full text Add to dashboard Cite

We have used electron paramagnetic resonance (EPR) to examine the structural impact of oxidizing specific methionine (M) side chains in calmodulin (CaM). It has been shown that oxidation of either M109 or M124 in CaM diminishes CaM regulation of the muscle calcium release channel, the ryanodine receptor (RyR), and that mutation of M to Q (glutamine) in either case produces functional effects identical to those of oxidation. Here we have used site-directed spin labeling and double electron-electron resonance (DEER), a pulsed EPR technique that measures distances between spin labels, to characterize the structural changes resulting from these mutations. Spin labels were attached to a pair of introduced cysteine residues, one in the C-lobe (T117C) and one in the N-lobe (T34C) of CaM, and DEER was used to determine the distribution of interspin distances. Ca binding induced a large increase in the mean distance, in concert with previous x-ray crystallography and NMR data, showing a closed structure in the absence of Ca and an open structure in the presence of Ca. DEER revealed additional information about CaM’s structural heterogeneity in solution: In both the presence and absence of Ca, CaM populates both structural states, one with probes separated by ~4 nm (closed) and another at ~6 nm (open). Ca shifts the structural equilibrium constant toward the open state by a factor of 13. DEER reveals the distribution of interprobe distances, showing that each of these states is itself partially disordered, with the width of each population ranging from 1.5 to 3 nm. Both mutations (M109Q and M124Q) decrease the effect of Ca on the structure of CaM, primarily by decreasing the closed-to-open equilibrium constant in the presence of Ca. We propose that Met oxidation alters CaM’s functional interaction with its target proteins by perturbing this Ca-dependent structural shift.

show abstract

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

Cited by 19 publications

References 50 publications

The myosin super-relaxed state is disrupted by estradiol deficiency

The myosin super-relaxed state is disrupted by estradiol deficiency

Redox regulation of the actin cytoskeleton and its role in the vascular system

Impact of methionine oxidation on calmodulin structural dynamics

Contact Info

Product

Resources

About