The interaction of troponin‐I with the N‐terminal region of actin

Abstract

The interaction between troponin-I and actin that underlies thin-filament regulation in striated muscle has been studied using proton magnetic resonance spectroscopy. A restricted portion of skeletal muscle troponin-I (residues 96-116) has previously been shown to be capable of inhibiting the MgATPase activity of actomyosin in a manner enhanced by tropomyosin [Syska et al. (1976) Biochem. J. 153,375 -3871. On the basis of homologous spectral effects for signals of specific groups observed in different complexes formed using the native proteins and a variety of defined peptides, it is concluded that the segment of troponin-I which has inhibitory activity interacts with the N-terminal region of actin. The surface of contact of the inhibitory segment of troponin-I with actin involves two regions of the N-terminal of actin. These are located between residues 1-7 and 19-44. The data are discussed in the context of a structural mechanism for the inhibition of myosin ATPase activation.Contraction of vertebrate skeletal muscle is regulated by the interaction of calcium with the troponin complex located on the actin-containing thin filaments [l -31. The binding of calcium to troponin-C releases the inhibition of the MgATPase activity of actomyosin by troponin-I that is bound to actin. Present evidence suggests that activation may occur by release of the inhibition of one of the kinetic steps of ATP hydrolysis rather than by merely reversing a steric impediment to myosin-actin interaction [3 -51. A series of structural changes transmitted through troponin-I and troponin-T, the tropomyosin-binding subunit, is implicit in triggering contraction. To understand more fully the mechanism of action of the troponin complex, precise information is required about the surfaces of contact between its subunits and the other thin filament proteins.

Tropomyosin and Troponin Regulation of Wild Type and E93K Mutant Actin Filaments from Drosophila Flight Muscle

“…The amino acids in actin involved in stabilizing the off state have not been positively identified, but there is evidence for troponin I contacts on domains 1 and 2 of actin (16). This is compatible with reports that changes in the shape of domain 2 of actin are associated with regulation (17).…”

The importance of C‐terminal amino acid residues of actin to the inhibition of actomyosin ATPase activity by caldesmon and troponin I

“…According to the results presented in this paper the maximum inhibitory effect of both requires the integrity of the C-terminal portion of the actin polypeptide chain. Despite these similarities, due to the occupation by caldesmon and troponin I of nonidentical but sequential sites within the N-terminal region of actin [5,6], the detailed inhibitory mechanism of actomyosin ATPase is different. Whereas caldesmon weakens the interaction of actin with myosin [1,30] as a result of the competitive displacement of myosin heads from the same or partially overlappin 8 binding site(s) on actin [5], troponin I seems to be involved in the slowing down of the kinetic steps of ATP hydrolysis (P: release) by the troponin-tropomyosin complex that takes place after the actin-myosin association [1,5,29,31].…”

A Gain-of-Function Mutation in the M-domain of Cardiac Myosin-binding Protein-C Increases Binding to Actin

“…LK(R/K)XK) in H3 of the tri-helix bundle (21,49). Notably, this sequence occurs as part of a more extended sequence that bears homology to the inhibitory peptide of troponin I that binds actin (30). Because deletion of this sequence in the ⌬H3 mutant reduced the binding affinity of C1C2 for actin (Fig.…”