Regulatory and Cytoskeletal Proteins of Vertebrate Skeletal Muscle

Ohtsuki, Iwao; Maruyama, Kosçak; Ebashi, Setsuro

doi:10.1016/s0065-3233(08)60525-2

Cited by 199 publications

(107 citation statements)

References 252 publications

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“…When S1 was rapidly mixed with the thin filament, these domains moved with almost the same or slightly faster rates than those of S1 binding measured by light scattering. In most but not all aspects, the rates of movement of the troponin tail domain and of the TnT-TnI coiled-coil C terminus were very similar to those of certain TnI sites (N terminus, Cys-133, and C terminus) previously characterized (Shitaka, Y., Kimura Striated muscle contraction is regulated by troponin (Tn) 1 and tropomyosin (Tm) on actin filaments in response to intracellular Ca 2ϩ levels (1,2). Tm, an extended ␣-helical coiled-coil dimmer, binds end to end along the actin filament and covers seven actin monomers.…”

supporting

confidence: 57%

The Rates of Switching Movement of Troponin T between Three States of Skeletal Muscle Thin Filaments Determined by Fluorescence Resonance Energy Transfer

Shitaka

Kimura

Miki

2005

Journal of Biological Chemistry

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Troponin (Tn) plays the key roles in the regulation of striated muscle contraction. Tn consists of three subunits (TnT, TnC, and TnI). In combination with the stopped-flow method, fluorescence resonance energy transfer between probes attached to Cys-60 or Cys-250 of TnT and Cys-374 of actin was measured to determine the rates of switching movement of the troponin tail domain (Cys-60) and of the TnT-TnI coiled-coil C terminus (Cys-250) between three states (relaxed, closed, and open) of the thin filament. When the free Ca 2؉ concentration was rapidly changed, these domains moved with rates of ϳ450 and ϳ85 s ؊1 at pH 7.0 on Ca 2؉ up and down, respectively. When myosin subfragment 1 (S1) was dissociated from thin filaments by rapid mixing with ATP, these domains moved with a single rate constant of ϳ400 s ؊1 in the presence and absence of Ca 2؉ . The light scattering measurements showed that ATP-induced S1 dissociation occurred with a rate constant >800 s ؊1 . When S1 was rapidly mixed with the thin filament, these domains moved with almost the same or slightly faster rates than those of S1 binding measured by light scattering. In most but not all aspects, the rates of movement of the troponin tail domain and of the TnT-TnI coiled-coil C terminus were very similar to those of certain TnI sites (N terminus, Cys-133, and C terminus) previously characterized (Shitaka, Y., Kimura, C., Iio, T., and Miki, M. (2004) Biochemistry 43, 10739 -10747), suggesting that a series of conformational changes in the Tn complex during switching on or off process occurs synchronously.

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supporting

confidence: 57%

The Rates of Switching Movement of Troponin T between Three States of Skeletal Muscle Thin Filaments Determined by Fluorescence Resonance Energy Transfer

Shitaka

Kimura

Miki

2005

Journal of Biological Chemistry

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“…C ontraction of the vertebrate-striated muscles (i.e., skeletal and cardiac muscles) is regulated by Ca 2ϩ through its binding to a specific regulatory protein complex, troponin (Tn), which is distributed at regular intervals along the entire thin filament (1,2). Tn is a complex of three different proteins, troponin T (TnT; tropomyosin-binding component), troponin I (TnI; inhibitory component), and troponin C (TnC; Ca 2ϩ -binding component).…”

mentioning

confidence: 99%

Ca ²⁺ -desensitizing effect of a deletion mutation ΔK210 in cardiac troponin T that causes familial dilated cardiomyopathy

Morimoto

Harada

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

150

114

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A deletion mutation ⌬K210 in cardiac troponin T (cTnT) was recently found to cause familial dilated cardiomyopathy (DCM). To explore the effect of this mutation on cardiac muscle contraction under physiological conditions, we determined the Ca 2؉ -activated force generation in permeabilized rabbit cardiac muscle fibers into which the mutant and wild-type cTnTs were incorporated by using our TnT exchange technique. The free Ca 2؉ concentrations required for the force generation were higher in the mutant cTnTexchanged fibers than in the wild-type cTnT-exchanged ones, with no statistically significant differences in maximal force-generating capability and cooperativity. Exchanging the mutant cTnT into isolated cardiac myofibrils also increased the free Ca 2؉ concentrations required for the activation of ATPase. In contrast, a deletion mutation ⌬E160 in cTnT that causes familial hypertrophic cardiomyopathy (HCM) decreased the free Ca 2؉ concentrations required for force generation, just as in the case of the other HCM-causing mutations in cTnT. The results indicate that cTnT mutations found in the two distinct forms of cardiomyopathy (i.e., HCM and DCM) change the Ca 2؉ sensitivity of cardiac muscle contraction in opposite directions. The present study strongly suggests that Ca 2؉ desensitization of force generation in sarcomere is a primary mechanism for the pathogenesis of DCM associated with the deletion mutation ⌬K210 in cTnT.C ontraction of the vertebrate-striated muscles (i.e., skeletal and cardiac muscles) is regulated by Ca 2ϩ through its binding to a specific regulatory protein complex, troponin (Tn), which is distributed at regular intervals along the entire thin filament (1, 2). Tn is a complex of three different proteins, troponin T (TnT; tropomyosin-binding component), troponin I (TnI; inhibitory component), and troponin C (TnC; Ca 2ϩ -binding component). On Ca 2ϩ binding to TnC, a Ca 2ϩ -induced interaction of TnC with TnI relieves the inhibitory action of TnI exerted on the thin filament and enables the myosin head to cyclically interact with actin in the thin filament and generate force. The Ca 2ϩ sensitivity of muscle contraction is determined by the Ca 2ϩ -binding affinity of TnC, which is dynamically altered through interaction with TnI and TnT in the myofilament lattice (3-8).Mutations in genes for cardiac troponin T (cTnT) and cardiac troponin I (cTnI) have been found to cause familial hypertrophic cardiomyopathy (HCM), an autosomal dominant heart disease characterized by asymmetrical ventricular hypertrophy with a high incidence of sudden death in young adults (9). We have already examined the effects of eight HCM-linked cTnT mutations (I79N, R92Q, ⌬E160, E244D, R278C, and two truncated mutants produced by a splice donor site mutation Int15G 1 3A) and six HCM-linked cTnI mutations (R145G, R145Q, R162W, ⌬K183, G203S, and K206Q) on the contractile functions of cardiac muscle by using a technique for exchanging the exogenous Tn complex into skinned muscle fibers and isolated myofibrils. We found t...

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“…This interaction blocks the inhibitory action of TnI, allowing formation of the Mg2+-activated ATPase actomyosin complex, and ultimately leads to muscle contraction. The roles and interactions of proteins in the regulatory system of striated muscle have been studied extensively (Leavis & Gergely, 1984;Ohtsuki et al, 1986;Zot & Potter, 1987;Grabarek et al, 1992;Farah et al, 1 994).…”

mentioning

confidence: 99%

Quantification of the calcium‐induced secondary structural changes in the regulatory domain of troponin‐C

et al. 1994

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The backbone resonance assignments have been completed for the apo ('H and "N) and calcium-loaded ('H, IsN, and 13C) regulatory N-domain of chicken skeletal troponin-C (1-90), using multidimensional homonuclear and heteronuclear NMR spectroscopy. The chemical-shift information, along with detailed NOE analysis and 3JHNHa coupling constants, permitted the determination and quantification of the Ca2+-induced secondary structural change in the N-domain of TnC. For both structures, 5 helices and 2 short 0-strands were found, as was observed in the apo N-domain of the crystal structure of whole TnC (Herzberg 0, James MNG, 1988, JMol Biol 203:761-779). The NMR solution structure of the apo form is indistinguishable from the crystal structure, whereas some structural differences are evident when comparing the 2Ca2+ state solution structure with the apo one. The major conformational change observed is the straightening of helix-B upon Ca2+ binding. The possible importance and role of this conformational change is explored. Previous CD studies on the regulatory domain of TnC showed a significant Ca2+-induced increase in negative ellipticity, suggesting a significant increase in helical content upon Ca2+ binding. The present study shows that there is virtually no change in a-helical content associated with the transition from apo to the 2Ca2+ state of the N-domain of TnC. Therefore, the Ca2+-induced increase in ellipticity observed by CD does not relate to a change in helical content, but more likely to changes in spatial orientation of helices.Keywords: calcium; CD; NMR; regulatory domain of troponin-C; secondary structural change Troponin-C has a key role in muscle contraction of vertebrate striated muscle (skeletal and cardiac). The binding of Ca2+ to TnC induces a conformational change that affects the interaction between TnC, troponin-I (TnI), and troponin-T (TnT). This interaction blocks the inhibitory action of TnI, allowing formation of the Mg2+-activated ATPase actomyosin complex, and ultimately leads to muscle contraction. The roles and interactions of proteins in the regulatory system of striated muscle have been studied extensively (Leavis & Gergely, 1984; Ohtsuki et al.,

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Regulatory and Cytoskeletal Proteins of Vertebrate Skeletal Muscle

Cited by 199 publications

References 252 publications

The Rates of Switching Movement of Troponin T between Three States of Skeletal Muscle Thin Filaments Determined by Fluorescence Resonance Energy Transfer

The Rates of Switching Movement of Troponin T between Three States of Skeletal Muscle Thin Filaments Determined by Fluorescence Resonance Energy Transfer

Ca ²⁺ -desensitizing effect of a deletion mutation ΔK210 in cardiac troponin T that causes familial dilated cardiomyopathy

Quantification of the calcium‐induced secondary structural changes in the regulatory domain of troponin‐C

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Regulatory and Cytoskeletal Proteins of Vertebrate Skeletal Muscle

Cited by 199 publications

References 252 publications

The Rates of Switching Movement of Troponin T between Three States of Skeletal Muscle Thin Filaments Determined by Fluorescence Resonance Energy Transfer

The Rates of Switching Movement of Troponin T between Three States of Skeletal Muscle Thin Filaments Determined by Fluorescence Resonance Energy Transfer

Ca 2+ -desensitizing effect of a deletion mutation ΔK210 in cardiac troponin T that causes familial dilated cardiomyopathy

Quantification of the calcium‐induced secondary structural changes in the regulatory domain of troponin‐C

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Ca ²⁺ -desensitizing effect of a deletion mutation ΔK210 in cardiac troponin T that causes familial dilated cardiomyopathy