Different actin affinities of human cardiac essential myosin light chain isoforms

Morano, Ingo; Haase, Hannelore

doi:10.1016/s0014-5793(97)00390-6

Cited by 38 publications

(23 citation statements)

References 17 publications

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“…There is a Lys residue at position 2 of this construct (position 13 of wild-type HmAtELC) and a free A-N-terminus that could partake in the cross-linking reaction even if the bound state is rare. It should also be noted that two laboratories have reported rather dramatic effects of peptides encompassing residues 4Ϫ14 of HmAtELC [42] and rabbit skeletal A1-type ELC [43] on actin affinities and myofibrillar ATPase, respectively, consistent with our observations. Thus, we are able to locate the actin-binding site largely to within the N-terminal 11 residues of HmAtELC and establish a correlation between actin-binding and kinetic modulation.…”

Section: Discussionsupporting

confidence: 92%

The N‐terminus of A1‐type myosin essential light chains binds actin and modulates myosin motor function

Timson

Trayer

1998

European Journal of Biochemistry

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There are two isoforms (A1 and A2) of the myosin essential light chain (ELC) and consequently two isoenzymes of myosin subfragment 1 (S1), S1(A1) and S1(A2). The two isoenzymes differ in their kinetic properties with S1(A1) having a lower apparent K m for actin and a slower turnover of MgATP (k cat ) than S1(A2). The two forms of the ELC differ only at their N-termini where A1 has an additional 40-odd amino acids that are not present in A2.The human atrial ELC (an A1-type ELC) was overexpressed in Escherichia coli and purified by ammonium sulphate fractionation and ion-exchange chromatography. The recombinant ELC had actinactivated MgATPase kinetics similar to those for rabbit skeletal S1(A1) under the same conditions. Deletion of the first 45 amino acid residues resulted in an ELC similar to the rabbit skeletal A2 isoform and, when hybridised into S1, in S1(A2)-like kinetic properties. Results obtained with an ELC mutant that lacks the first 11 residues were intermediate between these two extremes but tending towards the S1(A2)-like phenotype.The wild-type ELC (both hybridised into S1 or free in solution) could be cross-linked to F-actin, whereas the deletion mutant lacking the first 45 amino acids could not. The deletion mutant lacking the first 11 amino acids cross-linked only poorly under the same conditions, consistent with the MgATPase data. We therefore conclude that these N-terminal eleven amino acids predominantly encode an actinbinding site which modulates the kinetics of the myosin motor. Furthermore, while free A1-type ELC cross-linked to both polymeric F-actin and the monomeric G-actin:DNase-I complex, the same ELC in S1(A1) could only cross-link to F-actin. This suggests that the light chain binds to a different actin monomer than the heavy chain.

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Section: Discussionsupporting

confidence: 92%

The N‐terminus of A1‐type myosin essential light chains binds actin and modulates myosin motor function

Timson

Trayer

1998

European Journal of Biochemistry

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“…A weaker actin-binding affinity was observed in ELC a compared with the ELC v isoform (55). 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.…”

Section: Elc-mediated Regulation Of Actin-myosin Interactionsmentioning

confidence: 88%

“…2B), ELC-actin interaction studies revealed isoform-specific differences. A weaker actin-binding affinity was observed in ELC a compared with the ELC v isoform (55). This difference in actin binding was thought to result from the faster cycling kinetics of cross-bridges containing ELC a (54,55).…”

Section: Elc-mediated Regulation Of Actin-myosin Interactionsmentioning

confidence: 96%

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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“…These results were consistent, as discussed by Fewell et al (Fewell et al, 1998), with the increased rates of muscle shortening and force production associated with the expression of MLC1E/A in the ventricles of human cardiomyopathic hearts (Morano et al, 1996), as a possible compensatory mechanism. The affinity of MLC1E/A for actin is lower than is the actin-affinity of slow-type MLC1 (Morano and Haase, 1997), possibly allowing more rapid crossbridge cycling and, thereby, providing a mechanism for faster contractile properties in fibers expressing MLC1E/A. This would suggest that MLC1E/A facilitates more rapid contractions in jaw-closing muscles.…”

Section: Mlc1e/a Is Expressed With Mhc-mmentioning

confidence: 97%

Masticatory (`superfast') myosin heavy chain and embryonic/atrial myosin light chain 1 in rodent jaw-closing muscles

Reiser

Bicer

Chen

et al. 2009

Journal of Experimental Biology

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SUMMARY Masticatory myosin is widely expressed among several vertebrate classes. Generally, the expression of masticatory myosin has been associated with high bite force for a carnivorous feeding style (including capturing/restraining live prey), breaking down tough plant material and defensive biting in different species. Masticatory myosin expression in the largest mammalian order, Rodentia, has not been reported. Several members of Rodentia consume large numbers of tree nuts that are encased in very hard shells, presumably requiring large forces to access the nutmeat. We, therefore, tested whether some rodent species express masticatory myosin in jaw-closing muscles. Myosin isoform expression in six Sciuridae species was examined, using protein gel electrophoresis, immunoblotting, mass spectrometry and RNA analysis. The results indicate that masticatory myosin is expressed in some Sciuridae species but not in other closely related species with similar diets but having different nut-opening strategies. We also discovered that the myosin light chain 1 isoform associated with masticatory myosin heavy chain, in the same four Sciuridae species, is the embryonic/atrial isoform. We conclude that rodent speciation did not completely eliminate masticatory myosin and that its persistent expression in some rodent species might be related to not only diet but also to feeding style.

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Different actin affinities of human cardiac essential myosin light chain isoforms

Cited by 38 publications

References 17 publications

The N‐terminus of A1‐type myosin essential light chains binds actin and modulates myosin motor function

The N‐terminus of A1‐type myosin essential light chains binds actin and modulates myosin motor function

Myosin essential light chain in health and disease

Masticatory (`superfast') myosin heavy chain and embryonic/atrial myosin light chain 1 in rodent jaw-closing muscles

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