The possible role of myosin A1 light chain in the weakening of actin–myosin interaction

Stȩpkowski, Dariusz; Efimova, Natalya; Paczyńska, Agnieszka; Moczarska, A; Nieznanska, Hanna; Kakol, I

doi:10.1016/s0167-4838(97)00031-9

Cited by 13 publications

(9 citation statements)

References 46 publications

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“…Characteristics were measured in low ionic strength conditions suitable for both motility and ATPase measurements. V max and K M values for porcine βmys are equivalent to our previous measurements and similar but lower than sHMM in low ionic strength conditions and where a truncated long skeletal ELC(A1) had slightly increased V max compared to control (35). Previously measured V max and K M values from porcine βmys at higher ionic strength differ due to the incompatibility of the ionic strength conditions (12).…”

Section: Discussionsupporting

confidence: 85%

N-Terminus of Cardiac Myosin Essential Light Chain Modulates Myosin Step-Size

Wang¹,

Ajtai²,

Kazmierczak

et al. 2015

Biochemistry

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Muscle myosin cyclically hydrolyzes ATP to translate actin. Ventricular cardiac myosin (βmys) moves actin with three distinct unitary step-sizes resulting from its lever-arm rotation and with step-frequencies that are modulated in a myosin regulation mechanism. The lever-arm associated essential light chain (vELC) binds actin by its 43 residue N-terminal extension. Unitary steps were proposed to involve the vELC N-terminal extension with the 8 nm step engaging the vELC/actin bond facilitating an extra ~19 degrees of lever-arm rotation while the predominant 5 nm step forgoes vELC/actin binding. A minor 3 nm step is the unlikely conversion of the completed 5 to the 8 nm step. This hypothesis was tested using a 17 residue N-terminal truncated vELC in porcine βmys (Δ17βmys) and a 43 residue N-terminal truncated human vELC expressed in transgenic mouse heart (Δ43αmys). Step-size and step-frequency were measured using the Qdot motility assay. Both Δ17βmys and Δ43αmys had significantly increased 5 nm step-frequency and coincident loss in the 8 nm step-frequency compared to native proteins suggesting the vELC/actin interaction drives step-size preference. Step-size and step-frequency probability densities depend on the relative fraction of truncated vELC and relate linearly to pure myosin species concentrations in a mixture containing native vELC homodimer, two truncated vELCs in the modified homodimer, and one native and one truncated vELC in the heterodimer. Step-size and step-frequency, measured for native homodimer and at two or more known relative fractions of truncated vELC, are surmised for each pure species by using a new analytical method.

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Section: Discussionsupporting

confidence: 85%

N-Terminus of Cardiac Myosin Essential Light Chain Modulates Myosin Step-Size

Wang¹,

Ajtai²,

Kazmierczak

et al. 2015

Biochemistry

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“…Conflicting results were reported by Stepkowski et al (89), where the NH 2 -terminal extension in the long ELC was shown to reduce rather than increase the affinity of myosin for actin. These experiments, however, were performed by utilizing HMM, a two-headed heavy meromyosin containing both myosin light chains, ELC and RLC, suggesting that a full understanding of the ELC-mediated actin-myosin interaction requires taking into account the cooperativity between the two myosin heads as well as potential interactions between ELC and RLC (83,89). The complexity of these protein-protein interactions was further suggested by Pliszka et al (67), who demonstrated that the NH 2 -terminal region of MLC1 not only interacts with actin but also with the MHC.…”

Section: Elc-mediated Regulation Of Actin-myosin Interactionsmentioning

confidence: 77%

“…This difference in actin binding was thought to result from the faster cycling kinetics of cross-bridges containing ELC a (54,55). Conflicting results were reported by Stepkowski et al (89), where the NH 2 -terminal extension in the long ELC was shown to reduce rather than increase the affinity of myosin for actin. These experiments, however, were performed by utilizing HMM, a two-headed heavy meromyosin containing both myosin light chains, ELC and RLC, suggesting that a full understanding of the ELC-mediated actin-myosin interaction requires taking into account the cooperativity between the two myosin heads as well as potential interactions between ELC and RLC (83,89).…”

Section: Elc-mediated Regulation Of Actin-myosin Interactionsmentioning

confidence: 91%

Myosin essential light chain in health and disease

Hernandez¹,

Jones²,

Guzman³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

115

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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“…At least 7 fibers were used for each group. 40,42,44). In contrast, two lines of Tg mouse studies show no effect on XB detachment kinetics (23,29,34).…”

Section: Discussionmentioning

confidence: 95%

Deletion of 1–43 amino acids in cardiac myosin essential light chain blunts length dependency of Ca²⁺sensitivity and cross-bridge detachment kinetics

Michael

Gollapudi

Ford

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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The role of cardiac myosin essential light chain (ELC) in the sarcomere length (SL) dependency of myofilament contractility is unknown. Therefore, mechanical and dynamic contractile properties were measured at SL 1.9 and 2.2 μm in cardiac muscle fibers from two groups of transgenic (Tg) mice: 1) Tg-wild-type (WT) mice that expressed WT human ventricular ELC and 2) Tg-Δ43 mice that expressed a mutant ELC lacking 1-43 amino acids. In agreement with previous studies, Ca(2+)-activated maximal tension decreased significantly in Tg-Δ43 fibers. pCa(50) (-log(10) [Ca(2+)](free) required for half maximal activation) values at SL of 1.9 μm were 5.64 ± 0.02 and 5.70 ± 0.02 in Tg-WT and Tg-Δ43 fibers, respectively. pCa(50) values at SL of 2.2 μm were 5.70 ± 0.01 and 5.71 ± 0.01 in Tg-WT and Tg-Δ43 fibers, respectively. The SL-mediated increase in the pCa(50) value was statistically significant only in Tg-WT fibers (P < 0.01), indicating that the SL dependency of myofilament Ca(2+) sensitivity was blunted in Tg-Δ43 fibers. The SL dependency of cross-bridge (XB) detachment kinetics was also blunted in Tg-Δ43 fibers because the decrease in XB detachment kinetics was significant (P < 0.001) only at SL 1.9 μm. Thus the increased XB dwell time at the short SL augments Ca(2+) sensitivity at short SL and thus blunts SL-mediated increase in myofilament Ca(2+) sensitivity. Our data suggest that the NH(2)-terminal extension of cardiac ELC not only augments the amplitude of force generation, but it also may play a role in mediating the SL dependency of XB detachment kinetics and myofilament Ca(2+) sensitivity.

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The possible role of myosin A1 light chain in the weakening of actin–myosin interaction

Cited by 13 publications

References 46 publications

N-Terminus of Cardiac Myosin Essential Light Chain Modulates Myosin Step-Size

N-Terminus of Cardiac Myosin Essential Light Chain Modulates Myosin Step-Size

Myosin essential light chain in health and disease

Deletion of 1–43 amino acids in cardiac myosin essential light chain blunts length dependency of Ca²⁺sensitivity and cross-bridge detachment kinetics

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The possible role of myosin A1 light chain in the weakening of actin–myosin interaction

Cited by 13 publications

References 46 publications

N-Terminus of Cardiac Myosin Essential Light Chain Modulates Myosin Step-Size

N-Terminus of Cardiac Myosin Essential Light Chain Modulates Myosin Step-Size

Myosin essential light chain in health and disease

Deletion of 1–43 amino acids in cardiac myosin essential light chain blunts length dependency of Ca2+sensitivity and cross-bridge detachment kinetics

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Deletion of 1–43 amino acids in cardiac myosin essential light chain blunts length dependency of Ca²⁺sensitivity and cross-bridge detachment kinetics