Crossbridge Head Detachment Rate Constants Determined from a Model that Explains the Behavior of Both Weakly-and Strongly-Binding Crossbridges

Schoenberg, Mark J.

doi:10.1007/978-1-4684-6039-1_47

Cited by 4 publications

(2 citation statements)

References 21 publications

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“…Our finding begs the obvious question; What is the nature of the synchronization or cooperativity in the myosin actions producing the translational sliding movement of actin? There is some recent evidence suggesting a coordinated activity between the two heads of a myosin molecule 32 , 33 . However, the coordination between the two heads of a single myosin molecule does not lead to the length independence of D m if individual myosin molecules with such double heads randomly interact with an actin filament.…”

Section: Discussionmentioning

confidence: 99%

Fluctuation of actin sliding over myosin thick filaments <i>in vitro</i>

et al. 2005

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It is customarily thought that myosin motors act as independent force-generators in both isotonic unloaded shortening as well as isometric contraction of muscle. We tested this assumption regarding unloaded shortening, by analyzing the fluctuation of the actin sliding movement over long native thick filaments from molluscan smooth muscle in vitro. This analysis is based on the prediction that the effective diffusion coefficient of actin, a measure of the fluctuation, is proportional to the inverse of the number of myosin motors generating the sliding movement of an actin filament, hence proportional to the inverse of the actin length, when the actions of the motors are stochastic and statistically independent. Contrary to this prediction, we found the effective diffusion coefficient to be virtually independent of, and thus not proportional to, the inverse of the actin length. This result shows that the myosin motors are not independent force-generators when generating the continuous sliding movement of actin in vitro and that the sliding motion is a macroscopic manifestation of the cooperative actions of the microscopic ensemble motors.

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Section: Discussionmentioning

confidence: 99%

Fluctuation of actin sliding over myosin thick filaments <i>in vitro</i>

et al. 2005

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“…It was proposed that these domains may interplay with the regulatory light chains by their proximity to this region 20 and may thus confer further regulatory input that might not be resolved with shorter protein fragments such as C0C1. Finally, which binding state of the two-headed myosin is affected by MyBP-C and whether intermediate states such as the weakly bound crossbridges 58 are involved can now be resolved using more refined techniques at the ultrastructural and singlemolecule level.…”

Section: Cycling Of Myosin Heads Is Controlled By the Mybp-c Regulatomentioning

confidence: 99%

Myosin Binding Protein C, a Phosphorylation-Dependent Force Regulator in Muscle That Controls the Attachment of Myosin Heads by Its Interaction With Myosin S2

Kunst

Kress²,

Gruen³

et al. 2000

Circulation Research

205

220

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Abstract-Myosin binding protein C (MyBP-C) is one of the major sarcomeric proteins involved in the pathophysiology of familial hypertrophic cardiomyopathy (FHC). The cardiac isoform is tris-phosphorylated by cAMP-dependent protein kinase (cAPK) on ␤-adrenergic stimulation at a conserved N-terminal domain (MyBP-C motif), suggesting a role in regulating positive inotropy mediated by cAPK. Recent data show that the MyBP-C motif binds to a conserved segment of sarcomeric myosin S2 in a phosphorylation-regulated way. Given that most MyBP-C mutations that cause FHC are predicted to result in N-terminal fragments of the protein, we investigated the specific effects of the MyBP-C motif on contractility and its modulation by cAPK phosphorylation. The diffusion of proteins into skinned fibers allows the investigation of effects of defined molecular regions of MyBP-C, because the endogenous MyBP-C is associated with few myosin heads. Furthermore, the effect of phosphorylation of cardiac MyBP-C can be studied in a defined unphosphorylated background in skeletal muscle fibers only. Triton skinned fibers were tested for maximal isometric force, Ca 2ϩ /force relation, rigor force, and stiffness in the absence and presence of the recombinant cardiac MyBP-C motif. The presence of unphosphorylated MyBP-C motif resulted in a significant (1) depression of Ca 2ϩ -activated maximal force with no effect on dynamic stiffness, (2) increase of the Ca 2ϩ sensitivity of active force (leftward shift of the Ca 2ϩ /force relation), (3) increase of maximal rigor force, and (4) an acceleration of rigor force and rigor stiffness development. Tris-phosphorylation of the MyBP-C motif by cAPK abolished these effects. This is the first demonstration that the S2 binding domain of MyBP-C is a modulator of contractility. The anchorage of the MyBP-C motif to the myosin filament is not needed for the observed effects, arguing that the mechanism of MyBP-C regulation is at least partly independent of a "tether," in agreement with a modulation of the head-tail mobility. Soluble fragments occurring in FHC, lacking the spatial specificity, might therefore lead to altered contraction regulation without affecting sarcomere structure directly. (Circ Res. 2000;86:51-58.)

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Ferenczi¹

2000

Biotechnology Letters

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Crossbridge Head Detachment Rate Constants Determined from a Model that Explains the Behavior of Both Weakly-and Strongly-Binding Crossbridges

Cited by 4 publications

References 21 publications

Fluctuation of actin sliding over myosin thick filaments <i>in vitro</i>

Fluctuation of actin sliding over myosin thick filaments <i>in vitro</i>

Myosin Binding Protein C, a Phosphorylation-Dependent Force Regulator in Muscle That Controls the Attachment of Myosin Heads by Its Interaction With Myosin S2

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