Caldesmon inhibits skeletal actomyosin subfragment-1 ATPase activity and the binding of myosin subfragment-1 to actin.

Chalovich, Joseph M.; Cornelius, Peter; Benson, C E

doi:10.1016/s0021-9258(18)45633-5

Cited by 102 publications

(33 citation statements)

References 47 publications

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“…In both of these possible mechanisms, the N-terminal region of actin has important regulatory consequences, but it is less important in determining the affinity of binding. Also, both models are consistent with our earlier observations on the competition between S-l-ATP and caldesmon (Chalovich et al, 1987;Velaz etal., 1989;Marston & Redwood, 1992). This does not preclude the possibility of additional cooperative effects in the inhibition of ATPase activity.…”

Section: Discussionsupporting

confidence: 93%

“…A first step in understanding the molecular basis of this control mechanism is to determine how caldesmon interacts with actin and myosin. Several studies indicate that caldesmon inhibits the binding of myosin-ATP to actin, irrespective of the source of myosin, possibly by competing with myosin for overlapping binding sites on actin2 (Chalovich et al, 1987;Hemric et al, 1988;Velaz et al, 1989;Horiuchi et al, 1989;Brenner et al, 1991;Nowaket al, 1989;Bartegii etal., 1990;Haeberle etal., 1992). One proposed area of overlap between 0006-2960/94/0433-3210$04.50/0 caldesmon and S-l-ATP is the N-terminus of actin, particularly the first seven residues.…”

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confidence: 99%

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Caldesmon, N-Terminal Yeast Actin Mutants, and the Regulation of Actomyosin Interactions

Crosbie

Miller²,

Chalovich³

et al. 1994

Biochemistry

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N-Terminal yeast actin mutants were used to assess the role of N-terminal acidic residues in the interactions of caldesmon with actin. The yeast actins differed only in their N-terminal charge: wild type, two negative charges; 4Ac, four negative charges; DNEQ, neutral charge; delta DSE, one positive charge. Caldesmon inhibition of actomyosin subfragment 1 ATPase was affected by alterations in the N-terminus of actin. This inhibition was similar for skeletal muscle alpha-actin and the yeast 4Ac and wild-type actins (80%), but much smaller for the neutral and deletion mutants (15%). However, cosedimentation experiments revealed similar binding of caldesmon to polymerized rabbit skeletal muscle alpha-actin and each yeast actin. This result shows that the N-terminal acidic residues of actin are not required for the binding of caldesmon to F-actin. Caldesmon-actin interactions were also examined by monitoring the polymerization of G-actin induced by caldesmon. Although the final extent of polymerization was similar for all actins tested, the rates of polymerization differed. Skeletal muscle and 4Ac actins had similar rates of polymerization, and the wild-type actin polymerized at a slower rate. The neutral and deletion mutants had even slower rates of polymerization by caldesmon. The slow polymerization of DNEQ G-actin was traced to a greatly reduced binding of caldesmon to this mutant G-actin when compared to wild-type and alpha-actin. MgCl2-induced actin polymerization proceeded at identical rates for all actins.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Discussionsupporting

confidence: 93%

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confidence: 99%

Caldesmon, N-Terminal Yeast Actin Mutants, and the Regulation of Actomyosin Interactions

Crosbie

Miller²,

Chalovich³

et al. 1994

Biochemistry

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“…Smooth muscle tropomyosin is thus unlikely to participate in steric hindrance of myosin binding in EGTA. Caldesmon itself has been suggested to inhibit myosin binding by a steric mechanism (Chalovich et al, 1987;Velaz et al, 1990); our reconstructions would be consistent with the idea that caldesmon's COOH-terrninal region alone may be responsible for competing with myosin binding to discrete aetin molecules occurring on the thin filaments at ,,0800 ]~ intervals, but there is no evidence from our work of steric interference by caldesmon over the intervening 13-14 actin molecules (of. Marston and Redwood, 1993).…”

Section: Discussionsupporting

confidence: 79%

Three-dimensional reconstruction of caldesmon-containing smooth muscle thin filaments.

Vibert

Craig

Lehman

1993

The Journal of Cell Biology

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Abstract. Caldesmon is known to inhibit actomyosinATPase and filament sliding in vitro, and may play a role in modulating smooth muscle contraction as well as in diverse cellular processes including cytokinesis and exocytosis. However, the structural basis of caldesmon action has not previously been apparent. We have recorded electron microscope images of negatively stained thin filaments containing caldesmon and tropomyosin which were isolated from chicken gizzard smooth muscle in EGTA. Three-dimensional helical reconstructions of these filaments show actin monomers whose bilobed shape and connectivity are very similar to those previously seen in reconstructions of frozen-hydrated skeletal muscle thin filaments. In addition, a continuous thin strand of density follows the long-pitch actin helices, in contact with the inner domain of each actin monomer. Gizzard thin filaments treated with Ca2+/calmodulin, which dissociated caldesmon but not tropomyosin, have also been reconstructed. Under these conditions, reconstructions also reveal a bilobed actin monomer, as well as a continuous surface strand that appears to have moved to a position closer to the outer domain of actin. The strands seen in both EGTA-and Ca2+/calmodulin-treated illaments thus presumably represent tropomyosin. It appears that caldesmon can fix tropomyosin in a particular position on actin in the absence of calcium. An influence of caldesmon on tropomyosin position might, in principle, account for caldesmon's ability to modulate actomyosin interaction in both smooth muscles and non-muscle cells.

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“…In the case of actin-tropomyosin-caldesmon, it is the caldesmon that is responsible for inhibition of the rate of binding of S1 to actin (Sen et al, 2001). Furthermore, tropomyosin-troponin has a much greater effect on the equilibrium binding of activating states (i.e., S1-ADP and S1) than on nonactivating states, whereas caldesmon has its greatest effect on the equilibrium binding of nonactivating states (Chalovich et al, 1987). Tropomyosin may actually enhance the ability of caldesmon to compete with activating S1 binding to actin (Chen and Chalovich, 1992).…”

Section: Discussionmentioning

confidence: 99%

Troponin-Tropomyosin: An Allosteric Switch or a Steric Blocker?

Resetar

Stephens²,

Chalovich

2002

Biophysical Journal

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The interaction of myosin subfragment 1 (S1) with actin-tropomyosin-troponin (regulated actin) is highly nucleotide dependent. The binding of S1 or S1-ADP (but not S1-ATP nor N,N'-rho-phenylenedimaleimide-modified S1-ATP) to regulated actin activates ATP hydrolysis even in the absence of Ca(2+). Investigations with S1 and S1-ADP have led to the idea that some actin sites are directly blocked toward the binding of S1 either by tropomyosin or troponin. The blocked state is thought to occur only at ionic strengths greater than 50 mM. The question is whether nonactivating S1 binding is blocked under the same conditions. We show that troponin inhibits binding of the nonactivating state, N,N'-rho-phenylenedimaleimide-S1-ATP, to actin but only when tropomyosin is absent. A lag in the rate of binding of activating S1 to actin (an indicator of the blocked state) occurs only in the presence of tropomyosin. Thus, tropomyosin inhibits binding of rigor S1 but not S1-ATP-like states. No evidence for an ionic strength-dependent change in the mechanism of regulation was observed either from measurements of the rate of activating S1 binding or from the equilibrium binding of nonactivating S1 to actin. At all conditions examined, N,N'-rho-phenylenedimaleimide-S1-ATP bound to regulated actin in the absence of Ca(2+). These results support the view of regulation in which tropomyosin movement is an allosteric switch that is modulated by activating myosin binding but that does not function solely by regulating myosin binding.

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Caldesmon inhibits skeletal actomyosin subfragment-1 ATPase activity and the binding of myosin subfragment-1 to actin.

Cited by 102 publications

References 47 publications

Caldesmon, N-Terminal Yeast Actin Mutants, and the Regulation of Actomyosin Interactions

Caldesmon, N-Terminal Yeast Actin Mutants, and the Regulation of Actomyosin Interactions

Three-dimensional reconstruction of caldesmon-containing smooth muscle thin filaments.

Troponin-Tropomyosin: An Allosteric Switch or a Steric Blocker?

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