Thin Filament Proteins and Thin Filament-Linked Regulation of Vertebrate Muscle Contractio

Leavis, Paul C.; Gergely, J.; Szent‐Györgyi, Albert

doi:10.3109/10409238409108717

Cited by 409 publications

(231 citation statements)

References 388 publications

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“…Although striated muscle tropomyosin is constructed from an mRNA derived from nine coding exons (Ruiz-Opazo et al, 1985), structural domains are not apparent in the 400-A a-helical coiled-coil molecule, which is continuous and uninterrupted except possibly for several residues at the ends (Phillips et al, 1986). Yet there are specific interactions with other proteins of the muscle thin filament, whereby one tropomyosin molecule interacts with seven contiguous actin subunits and one troponin complex (Leavis & Gergely, 1984;Zot & Potter, 1987). Differential calorimetric studies of striated aa-tropomyosin have been interpreted as having seven unfolding domains (Potekhin & 1982), suggesting a relationship to actin binding sites.…”

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confidence: 99%

Unfolding domains of recombinant fusion αα‐tropomyosin

et al. 1992

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The thermal unfolding of the coiled-coil a-helix of recombinant acu-tropomyosin from rat striated muscle containing an additional 80-residue peptide of influenza virus NSI protein at the N-terminus (fusion-tropomyosin) was studied with circular dichroism and fluorescence techniques. Fusion-tropomyosin unfolded in four cooperative transitions: (1) a pretransition starting at 35 "C involving the middle of the molecule; (2) a major transition at 46 "C involving no more than 36% of the helix from the C-terminus; (3) a major transition at 56 "C involving about 46% of the helix from the N-terminus; and (4) a transition from the nonhelical fusion domain at about 70 "C. Rabbit skeletal muscle tropomyosin, which lacks the fusion peptide but has the same tropomyosin sequence, does not exhibit the 56 "C or 70 "C transition. The very stable fusion unfolding domain of fusion-tropomyosin, which appears in electron micrographs as a globular structural domain at one end of the tropomyosin rod, acts as a crosslink to stabilize the adjacent N-terminal domain. The least stable middle of the molecule, when unfolded, acts as a boundary to allow the independent unfolding of the C-terminal domain at 46 "C from the stabilized N-terminal unfolding domain at 56 "C. Thus, strong localized interchain interactions in coiled-coil molecules can increase the stability of neighboring domains.

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Unfolding domains of recombinant fusion αα‐tropomyosin

et al. 1992

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“…protein TnC-TnI interactions are essential during the activation of muscle and the modifications in these interactions following Ca2+ binding to TnC very likely initiate the signal that triggers contraction [20]. Three patches each of 11 residues (nos 50-60, 90-100, 126-136) have been identified on skeletal TnC for TnC-TnI interactions .…”

Section: Structural Requirements Of the And+-bindingmentioning

confidence: 99%

Characterization of the Ca²⁺‐switch in skeletal and cardiac muscles

1989

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To determine the significance of the global structure of the regulatory proteins in the mechanism of the Ca*+-switch in cardiac and skeletal muscle contractions, the properties of a family of Ca Z+-binding proteins with 4 or 3 EF-hand motifs have been studied with desensitized skinned fiber preparations. Proteins with 4 EF hands (such as troponins C -TnCs) are dumb-bell shaped, those with 3 EF hands (parvalbumin) being ellipsoidal. The number of active sites varied between four and two. We find that the ability to anchor in the fiber is limited to proteins with 4 EF hands and, at least, two active Caz+-binding sites, one each in the N-and C-termini. The results suggest that the dumb-bell shaped global structure is critical for the switching action in muscular contraction, and a trigger site in the N-terminus and a structural site in the C-terminus need to be active in order to regulate contractility.

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“…Since tropomyosin functions as a component of the microfilament system (Leavis and Gergely, 1984), the physiological significance of elevated synthesis of tropomyosin-1 is uncertain. A more relevant question is whether such elevated expression is reflected in increased utilization of tropomyosin-1 in the cytoskeleton with attendant alteration in cytoskeletal composition.…”

Section: Cytoskeletal Utilization Of Tropomyosin-1 In Dt and Nih3t3 Lmentioning

confidence: 99%

“…Tropomyosin, in its native form, occurs as a side-to-side dimer. The dimers polymerize end-to-end in associating with filamentous actin in microfilaments (Leavis and Gergely, 1984). Several studies have shown that the thermodynamically favored dimer is a heterodimer of two tropomyosin isoforms (e.g.…”

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confidence: 99%

“…Tropomyosins are a family of ubiquitous actin-binding proteins with extensive a-helical structure that play a welldefined role in muscle contraction (Leavis and Gergely, 1984 ;Payne and Rudnick, 1985 ;Lees-Miller and Helfman, 1991). In non-muscle cells, the role of tropomyosins is less clearly understood, and it is generally thought that they are involved in stabilization of actin microfilaments which, in turn, play an important role in maintaining cell shape, motil-ity, and interaction with extracellular supporting elements (Pollard et al, 1976;CBtC, 1983;Stossel et al, 1985).…”

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Expression, Cytoskeletal Utilization and Dimer Formation of Tropomyosin Derived from Retroviral‐Mediated cDNA Transfer

Prasad

Fuldner

Braverman

et al. 1994

European Journal of Biochemistry

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Expression of the tropomyosin-1 isoform was enhanced by cDNA transfer in non-transformed murine 3T3 fibroblasts and also in v-Ki-ras transformed fibroblasts in which native tropomyosin-1 expression had been reduced and tropomyosin-2 synthesis virtually eliminated by action of the oncogene. The level of synthesis of insert-derived tropomyosin-1 was similar in normal and transformed transductants (3 -5 times normal levels). The high level of insert-derived tropomyosin-1 expression resulted in a considerable increase in tropomyosin-1 utilization in the cytoskeleton of transformed cells, but this expression still did not reach normal levels, suggesting an oncogenerelated inhibition of tropomyosin utilization. A large proportion of newly synthesized native tropomyosin-1 in normal, unmodified fibroblasts appeared in homodimers which, upon prolonged incubation, were largely converted to the heterodimers. Excess tropomyosin-1 derived from the inserted cDNA also appeared largely as the homodimer in both normal and transformed cells. This homodimer was utilized effectively in the formation of cytoskeletal structures but was partially converted to heterodimer by chain exchange. Under steady-state conditions, approximately 33 % of the cytoskeletal tropomyosin-1 -containing dimers were homodimers, compared to approximately 10% in normal fibroblasts. The results show that the increased amount of tropomyosin-1 homodimer entering the cytoskeleton under conditions of tropomyosin-1 excess, results in an atypical microfilament composition. The effect of this excess of tropomyosin-1 homodimers on stability or function of microfilament fibers remains to be determined. The results also confirm that the mechanisms of rapid homodimer formation with conversion to heterodimers by chain exchange, known from in vitro studies, also occur in vivo.

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Thin Filament Proteins and Thin Filament-Linked Regulation of Vertebrate Muscle Contractio

Cited by 409 publications

References 388 publications

Unfolding domains of recombinant fusion αα‐tropomyosin

Unfolding domains of recombinant fusion αα‐tropomyosin

Characterization of the Ca²⁺‐switch in skeletal and cardiac muscles

Expression, Cytoskeletal Utilization and Dimer Formation of Tropomyosin Derived from Retroviral‐Mediated cDNA Transfer

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Thin Filament Proteins and Thin Filament-Linked Regulation of Vertebrate Muscle Contractio

Cited by 409 publications

References 388 publications

Unfolding domains of recombinant fusion αα‐tropomyosin

Unfolding domains of recombinant fusion αα‐tropomyosin

Characterization of the Ca2+‐switch in skeletal and cardiac muscles

Expression, Cytoskeletal Utilization and Dimer Formation of Tropomyosin Derived from Retroviral‐Mediated cDNA Transfer

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Characterization of the Ca²⁺‐switch in skeletal and cardiac muscles