Truncation of Vertebrate Striated Muscle Myosin Light Chains Disturbs Calcium-Induced Structural Transitions in Synthetic Myosin Filaments

Podlubnaya, Z. A.; Kakol, I; Moczarska, A; Stȩpkowski, Dariusz; Udaltsov, S. N.

doi:10.1006/jsbi.2000.4265

Cited by 9 publications

(4 citation statements)

References 42 publications

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“…For example, cleavage modifications of MLC-2v in rabbit ventricular tissue are associated with myocardial stunning attributable to reversible ischemic injury 14,15. The cleavage of N-terminal residues is associated with impaired myosin-actin interaction, thereby limiting force generation and Ca 2+ sensitivity, both prominent features of CP/CPB-induced myocardial stunning 16,17. In our study, similar alterations were observed in the atrial specific MLC-2a (Spot 2, Table 1).…”

Section: Discussionmentioning

confidence: 99%

Pilot Proteomic Profile of Differentially Regulated Proteins in Right Atrial Appendage Before and After Cardiac Surgery Using Cardioplegia and Cardiopulmonary Bypass

et al. 2008

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Background-Although highly protective, cardiac surgery using cardioplegia and cardiopulmonary bypass (CP/CPB) subjects myocardium to hypothermic reversible ischemic injury that can impair cardiac function which results in a greatly enhanced risk of mortality. Acute changes in myocardial contractile activity are likely regulated via protein modifications. We performed the following study to determine changes in the protein profile of human myocardium following CP/CPB. Methods and Results-Right atrial appendage was collected from 8 male patients pre and post-CP/CPB. Atrial tissue lysates were subjected to 2-dimensional electrophoresis, total protein staining, gel averaging, and quantitative densitometry. Ten prominent spots regulated in response to CP/CPB were identified using mass spectrometry. Two hundred twenty-five and 256 protein spots were reliably detected in 2D-gels from pre-and post-CP/CPB patients, respectively. Five unique (ie, not detected post-CP/CPB) and 17 significantly increased spots were detected pre-CP/CPB. Thirty-four unique and 25 significantly increased spots were detected in the post-CP/CPB group. Identified proteins that changed after CP/CPB included: MLC-2a, ATP-synthase delta chain and Enoyl-CoenzymeA hydratase, glutathione-s-transferase omega, ␣-1-acid-glycoprotein, and phosphatidylethanolamine-binding protein. Conclusions-Cardiac

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Section: Discussionmentioning

confidence: 99%

Pilot Proteomic Profile of Differentially Regulated Proteins in Right Atrial Appendage Before and After Cardiac Surgery Using Cardioplegia and Cardiopulmonary Bypass

et al. 2008

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“…The functional significance of the NH 2 -terminal region of ELC was also shown with ELC deletion mutants. Using electron microscopy and synthetic myosin filaments, Podlubnaya et al (69) showed that removal of 13 amino acids from the NH 2 -terminus of rabbit skeletal and/or cardiac muscle ELC is responsible for ablation of the Ca 2ϩ -induced mobility of the myosin subfragment-2 (S2) region. The movement of myosin S2 together with the myosin head (S1) on the surface of the synthetic myosin filaments was only observed for the native compared with truncated ELC mutant proteins (68 -70).…”

Section: Function Of Nh 2 -Terminus Of Elcmentioning

confidence: 99%

Myosin essential light chain in health and disease

Hernandez¹,

Jones²,

Guzman³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

117

113

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The essential light chain of myosin (ELC) is known to be important for structural stability of the ␣-helical lever arm domain of the myosin head, but its function in striated muscle contraction is poorly understood. Two ELC isoforms are expressed in fast skeletal muscle, a long isoform and its NH 2-terminal ϳ40 amino acid shorter counterpart, whereas only the long ELC is observed in the heart. Biochemical and structural studies revealed that the NH 2-terminus of the long ELC can make direct contacts with actin, but the effects of the ELC on the affinity of myosin for actin, ATPase, force, and the kinetics of force generating myosin cross-bridges are inconclusive. Myosin containing the long ELC has been shown to have slower cross-bridge kinetics than myosin with the short isoform. A difference was also reported among myosins with long isoforms. Increased shortening velocity was observed in atrial compared with ventricular muscle fibers. The common findings suggest that ELC provides the fine tuning of the myosin motor function, which is regulated in an isoform and tissue-dependent manner. The functional importance of the ELC is further implicated by the discovery of ELC mutations associated with Familial Hypertrophic Cardiomyopathy. The pathological phenotypes vary in severity, but more notably, almost all ELC mutations result in sudden cardiac death at a young age. This review summarizes the functional roles of striated muscle ELC in normal healthy muscle and in disease. Transgenic animal models and phenotypic characterization of ELC-mediated remodeling of the heart are also discussed.cross-bridge kinetics; striated muscle contraction; familial hypertrophic cardiomyopathy; sarcomeric mutations; failing heart; sudden cardiac death STRIATED MUSCLE MYOSIN

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“…A. Podlubnaya, Malyshev, et al 2000; Z. Podlubnaya et al 1999; Z. A. Podlubnaya, Kąkol, et al 2000) , and by phosphorylation (Heling, Geeves, and Kad 2020; Colson et al 2010; Levine et al 1996; Ponnam et al 2019; McNamara, Singh, and Sadayappan 2019).…”

Section: Introductionmentioning

confidence: 98%

“…This suggests that the ancillary myosin binding proteins could assist in generating order on the thick filament backbone. Myosin’s biochemical activity is mediated by load (Linari et al 2015; Fusi et al 2016), by direct calcium binding to both thin and thick filaments (Ma et al 2023; Lehman and Kendrick-Jones 1973; Bremel and Weber 1975; Z. A. Podlubnaya, Malyshev, et al 2000; Z.…”

Section: Introductionmentioning

confidence: 99%

Spatially resolving how phosphorylation affects ß-cardiac myosin activity in porcine myofibril sarcomeres with single molecule resolution

Pilagov,

Steczina,

Naim

et al. 2024

Preprint

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Cardiac muscle contraction is mediated by myosin binding from the thick filament of the sarcomere to the thin filament in an ATP powered reaction. This process is highly regulated on a beat-to-beat basis by calcium interactions with the thin filament. Additionally, the number of heads available for participation in contraction is also regulated, resulting in a dynamically variable reserve of heads for controlling contractile force. We aimed to discover the size of this reserve and how it is modulated by phosphorylation. Using single molecule imaging of fluorescently labelled ATP molecules binding and releasing myosins within porcine cardiac sarcomeres, we could determine myosin activity with high spatial resolution. We find three kinetic species when examining the myosin ATPase. The fastest is consistent with non-specific ATP binding to myosin’s surface, and the slower two species are consistent with the previously identified DRX and SRX states. The former is thought to represent myosins in an ON state, ready to interact with the thin filament and the latter an OFF state with slowed ATPase that constitutes the cardiac reserve. We find that the cardiac reserve is 50% in the sarcomere and this can be sub-divided into the P-, C- and D-zones, with the D-zone having the least population of OFF heads (44%). Treatment with PKA phosphorylates cardiac myosin binding protein-C (cMyBP-C) leading to a 16% reduction in reserve in the C-zone (where cMyBP-C is found), a 10% reduction in the P-zone, and an unexpected 8% increase in the D-zone. By contrast, myosin regulatory light chain (RLC) phosphorylation with myosin light chain kinase (MLCK) resulted in a large 24% decrease in reserve myosins, interestingly the least affected area of the sarcomere was the C-zone. Altogether these data suggest that cMyBP-C’s interaction with RLC governs the degree of activation due to RLC phosphorylation.

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Truncation of Vertebrate Striated Muscle Myosin Light Chains Disturbs Calcium-Induced Structural Transitions in Synthetic Myosin Filaments

Cited by 9 publications

References 42 publications

Pilot Proteomic Profile of Differentially Regulated Proteins in Right Atrial Appendage Before and After Cardiac Surgery Using Cardioplegia and Cardiopulmonary Bypass

Pilot Proteomic Profile of Differentially Regulated Proteins in Right Atrial Appendage Before and After Cardiac Surgery Using Cardioplegia and Cardiopulmonary Bypass

Myosin essential light chain in health and disease

Spatially resolving how phosphorylation affects ß-cardiac myosin activity in porcine myofibril sarcomeres with single molecule resolution

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