Fumiaki Yumoto

The University of Tokyo, Tokyo, Tokyo-to, Japan

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Publications (28)85.79 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Plastins are Ca(2+)-regulated actin-bundling proteins, and essential for developing and stabilizing actin cytoskeletons. T-plastin is expressed in epithelial and mesenchymal cells of solid tissues, whereas L-plastin is expressed in mobile cells such as hemopoietic cell lineages and cancer cells. Using various spectroscopic methods, gel-filtration chromatography, and isothermal titration calorimetry, we here demonstrate that the EF-hand motifs of both T- and L-plastin change their structures in response to Ca(2+), but the sensitivity to Ca(2+) is lower in T-plastin than in L-plastin. These results suggest that T-plastin is suitable for maintaining static cytoskeletons, whereas L-plastin is suitable for dynamic rearrangement of cytoskeletons.
    Biochemical and Biophysical Research Communications 11/2012; · 2.28 Impact Factor
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    ABSTRACT: Abstract Troponin C (TnC) is the Ca2+-sensing subunit of troponin that triggers the contraction of striated muscles. In scallops, the striated muscles consume little ATP energy in sustaining strong contractile forces. The N-terminal domain of TnC works as the Ca2+ sensor in vertebrates, whereas scallop TnC uses the C-terminal domain as the Ca2+ sensor, suggesting that there are differences in the mechanism of the Ca2+-dependent regulation of muscles between invertebrates and vertebrates. Here, we report the crystal structure of the Akazara scallop adductor muscle TnC C-terminal domain (asTnCC) complexed with a short troponin I fragment (asTnIS) and Ca2+. The electron density of a Ca2+ ion is observed in only one of the two EF-hands. The EF-hands of asTnCC can only be in the fully open conformation with the assistance of asTnIS. The number of hydrogen bonds between asTnCC and asTnIS is markedly lower than the number in the vertebrate counterparts. The Ca2+ modulation on the binding between asTnCC and asTnIS is weaker, but structural change of the complex depending on Ca2+ concentration was observed. Together, these findings provide a detailed description of the distinct molecular mechanism of contractile regulation in the scallop adductor muscle from that of vertebrates.
    Biological Chemistry 08/2012; · 2.68 Impact Factor
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    ABSTRACT: Catechins, biologically active polyphenols in green tea, are known to have a protective effect against cardiovascular diseases. In this study, we investigated direct actions of green tea catechins on cardiac muscle function to explore their uses as potential drugs for cardiac muscle disease. The effects of catechins were systematically investigated on the force-pCa relationship in skinned cardiac muscle fibres to determine their direct effects on cardiac myofilament contractility. The mechanisms of action of effective catechins were investigated using troponin exchange techniques, quartz crystal microbalance, nuclear magnetic resonance and a transgenic mouse model. (-)-Epicatechin-3-gallate (ECg) and (-)-epigallocatechin-3-gallate (EGCg), but not their stereoismers (-)-catechin-3-gallate and (-)-gallocatechin-3-gallate, decreased cardiac myofilament Ca(2+) sensitivity probably through its interaction with cardiac troponin C. EGCg restored cardiac output in isolated working hearts by improving diastolic dysfunction caused by increased myofilament Ca(2+) sensitivity in a mouse model of hypertrophic cardiomyopathy. The green tea catechins, ECg and EGCg, are Ca(2+) desensitizers acting through binding to cardiac troponin C. These compounds might be useful compounds for the development of therapeutic agents to treat the hypertrophic cardiomyopathy caused by increased Ca(2+) sensitivity of cardiac myofilaments.
    British Journal of Pharmacology 11/2010; 161(5):1034-43. · 5.07 Impact Factor
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    ABSTRACT: Despite >50 years of research work since the discovery of sliding filament mechanism in muscle contraction, structural details of the coupling of cyclic cross-bridge movement to ATP hydrolysis are not yet fully understood. An example would be whether lever arm tilting on the myosin filament backbone will occur in the absence of actin. The most direct way to elucidate such movement is to record ATP-induced cross-bridge movement in hydrated thick filaments. Using the hydration chamber, with which biological specimens can be kept in an aqueous environment in an electron microscope, we have succeeded in recording ATP-induced cross-bridge movement in hydrated thick filaments consisting of rabbit skeletal muscle myosin, with gold position markers attached to the cross-bridges. The position of individual cross-bridges did not change appreciably with time in the absence of ATP, indicating stability of time-averaged cross-bridge mean position. On application of ATP, individual cross-bridges moved nearly parallel to the filament long axis. The amplitude of the ATP-induced cross-bridge movement showed a peak at 5-7.5 nm. At both sides of the filament bare region, across which the cross-bridge polarity was reversed, the cross-bridges were found to move away from, but not toward, the bare region. Application of ADP produced no appreciable cross-bridge movement. Because ATP reacts rapidly with the cross-bridges (M) to form complex (M x ADP x Pi) with an average lifetime >10 s, the observed cross-bridge movement is associated with reaction, M + ATP --> M x ADP x Pi. The cross-bridges were observed to return to their initial position after exhaustion of ATP. These results constitute direct demonstration of the cross-bridge recovery stroke.
    Proceedings of the National Academy of Sciences 12/2008; 105(45):17396-401. · 9.81 Impact Factor
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    ABSTRACT: Akazara scallop striated adductor muscle troponin C (TnC) binds only one Ca2+ because the three EF-hand motifs are short of critical residues for the coordination of Ca2+. Fourier-transform infrared spectroscopy was applied to study coordination structures of M2+ (= Mg2+, Ca2+, Sr2+, and Ba2+) bound in an Akazara scallop TnC mutant (E142D) and the wild-type TnC C-lobe in D2O solution. The region of the COO- antisymmetric stretch provides information regarding the coordination modes of a COO- group to a metal ion. The side chain COO- group of Asp142 did not bind to Ca2+ in the bidentate coordination mode, suggesting that the absence of a methylene group is critical for the Ca2+ coordination structure of Akazara scallop TnC (Nara et al., Vib Spect 2006, 42, 188-191). The present study has shown that the absence of a methylene group is not compensated for by a larger metal ion such as Sr2+ or Ba2+. CD spectra showed that the secondary structures are conserved between M2+-free (apo), Mg2+-loaded, Ca2+-loaded, Sr2+-loaded, and Ba2+-loaded states, which was consistent with the results estimated from their amide I band patterns. The metal-ligand interaction at position 12 of site IV is discussed in comparison with the coordination mode of the side chain COO- group of the wild-type TnC C-lobe.
    Biopolymers 08/2008; 89(7):595-9. · 2.88 Impact Factor
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    ABSTRACT: Akazara scallop (Chlamys nipponensis akazara) troponin C (TnC) of striated adductor muscle binds only one Ca(2+) ion at the C-terminal EF-hand motif (Site IV), but it works as the Ca(2+)-dependent regulator in adductor muscle contraction. In addition, the scallop troponin (Tn) has been thought to regulate muscle contraction via activating mechanisms that involve the region spanning from the TnC C-lobe (C-lobe) binding site to the inhibitory region of the TnI, and no alternative binding of the TnI C-terminal region to TnC because of no similarity between second TnC-binding regions of vertebrate and the scallop TnIs. To clarify the Ca(2+)-regulatory mechanism of muscle contraction by scallop Tn, we have analyzed the Ca(2+)-binding properties of the complex of TnC C-lobe and TnI peptide, and their interaction using isothermal titration microcalorimetry, nuclear magnetic resonance, circular dichroism, and gel filtration chromatography. The results showed that single Ca(2+)-binding to the Site IV leads to a structural transition not only in Site IV but also Site III through the structural network in the C-lobe of scallop TnC. We therefore assumed that the effect of Ca(2+)-binding must lead to a change in the interaction mode between the C-lobe of TnC and the TnI peptide. The change should be the first event of the transmission of Ca(2+) signal to TnI in Tn ternary complex.
    Biochemical and Biophysical Research Communications 05/2008; 369(1):109-14. · 2.28 Impact Factor
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    ABSTRACT: Plant respiratory burst oxidase homolog (rboh) proteins, which are homologous to the mammalian 91-kDa glycoprotein subunit of the phagocyte oxidase (gp91(phox)) or NADPH oxidase 2 (NOX2), have been implicated in the production of reactive oxygen species (ROS) both in stress responses and during development. Unlike mammalian gp91(phox)/NOX2 protein, plant rboh proteins have hydrophilic N-terminal regions containing two EF-hand motifs, suggesting that their activation is dependent on Ca(2+). However, the significance of Ca(2+) binding to the EF-hand motifs on ROS production has been unclear. By employing a heterologous expression system, we showed that ROS production by Arabidopsis thaliana rbohD (AtrbohD) was induced by ionomycin, which is a Ca(2+) ionophore that induces Ca(2+) influx into the cell. This activation required a conformational change in the EF-hand region, as a result of Ca(2+) binding to the EF-hand motifs. We also showed that AtrbohD was directly phosphorylated in vivo, and that this was enhanced by the protein phosphatase inhibitor calyculin A (CA). Moreover, CA itself induced ROS production and dramatically enhanced the ionomycin-induced ROS production of AtrbohD. Our results suggest that Ca(2+) binding and phosphorylation synergistically activate the ROS-producing enzyme activity of AtrbohD.
    Journal of Biological Chemistry 05/2008; 283(14):8885-92. · 4.65 Impact Factor
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    ABSTRACT: Troponin C (TnC) is the Ca(2+)-binding component of troponin and triggers muscle contraction. TnC of the invertebrate Akazara scallop can bind only one Ca(2+) at the C-terminal EF-hand motif. Recombinant TnC was expressed in Escherichia coli, purified, complexed with a 24-residue synthetic peptide derived from scallop troponin I (TnI) and crystallized. The crystals diffracted X-rays to 1.80 A resolution and belonged to space group P2(1)2(1)2(1), with unit-cell parameters a = 32.1, b = 42.2, c = 60.0 A. The asymmetric unit was assumed to contain one molecular complex of the Akazara scallop TnC C-lobe and TnI fragment, with a Matthews coefficient of 1.83 A(3) Da(-1) and a solvent content of 33.0%.
    Acta Crystallographica Section F Structural Biology and Crystallization Communications 07/2007; 63(Pt 6):535-7. · 0.55 Impact Factor
  • Fumiaki Yumoto, Masaru Tanokura
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    ABSTRACT: The Ca2+-regulation of scallop striated muscle contraction, a Ca2+-regulation mechanism that is linked to myosin, was first discovered by A. G. Szent-Györgyi and his colleagues. 1,2 In myosin-linked Ca2+-regulation, the Ca2+ -receptive site is the essential light chain of myosin, and the ATPase of the scallop myofibrils has been found to be desensitized to Ca2+ by removal of the regulatory light chain (RLC) of myosin in response to treatment with a divalent cation chelator (EDTA). At the same time, three components of troponin and tropomyosin have also been isolated from scallop striated muscle, and several of their biochemical properties have been investigated.3–5 In this troponin-linked Ca2+-regulation, the concurrent presence of all three components of troponin (troponins C, I, and T; TnC, TnI, and TnT) and tropomyosin are necessary for the regulation of actomyosin ATPase activity.6–10 The action of Ca2+ on TnC ultimately induces actomyosin ATPase activity. Troponin-linked Ca2+ -regulation is also desensitized by the removal of TnC in response to treatment with divalent cation chelators such as EDTA or CDTA. The mutual relation of these two types of Ca2+-regulations in scallop myofibrils was then investigated as follows.11 Desensitized scallop myofibrils were prepared by removing both RLC and TnC by treatment with a divalent cation chelator, CDTA, and the effects of reconstitution with RLC and/or TnC on the ATPase activity of the desensitized myofibrils were examined.
    Advances in experimental medicine and biology 02/2007; 592:163-73. · 1.83 Impact Factor
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    ABSTRACT: In summary, we have shown that the TnI-TnC-TnT2 ternary complex (-52 kDa) has a mobile actin-binding domain (-6.1 kDa) that tumbles independently of the core domain. By docking the mobile domain and the core domain into the cryo-EM map obtained for thin filaments at low Ca2+, a model for actin-troponin interaction has been obtained. This model shows the atomic details of interactions of actin with the mobile domain and suggests the mechanism by which troponin generates a shift in the azimuthal position of tropomyosin in response to changes in Ca2+ levels. In this model the mobile domain of troponin interacts with three actins and one troponin interacts with four actin molecules. The relationship between myosin and the mobile domain suggests that the latter may work as a fail-safe latch to secure a relaxed state. The model also provides insights into many mutations associated with human cardiomyopathy and has implications for the function of other actin-binding proteins. Coordinates of the mobile domain have been deposited in the Protein Data Bank under accession codes 1VDI (low Ca2+) and 1VDJ (high Ca2+). Chemical shifts of the mobile domain have been deposited in the BMRB under accession ID 18140.
    Advances in experimental medicine and biology 02/2007; 592:71-86. · 1.83 Impact Factor
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    ABSTRACT: The coordination structures of Ca(2+) ion bound to synthetic peptide analogues of the calcium-binding site III of rabbit skeletal muscle troponin C (TnC) were investigated by Fourier transform infrared (FTIR) spectroscopy. The region of the COO(-) antisymmetric stretching vibration provides information about the coordination modes of a COO(-) group to a metal ion. The 34-residue peptide corresponding to the EF hand motif (helix-loop-helix) showed a band at 1552 cm(-1) in the Ca(2+)-loaded state, indicating that the side-chain COO(-) group of Glu at the 12th position serves as a ligand for Ca(2+) in the bidentate coordination mode. On the other hand, the 13-residue peptide (Ac-DRDADGYIDAEEL-NH(2)) containing the Ca(2+)-binding site III (DRDADGYIDAEE) did not show such spectral patterns in the Ca(2+)-loaded state, meaning that shorter synthetic peptide corresponding to the site III has less or no affinity for Ca(2+). It was found that the 17-residue peptide (Ac-DRDADGYIDAEELAEIF-NH(2)) is the minimum peptide necessary for the interaction of side-chain COO(-)of Glu at the 12th position with Ca(2+) in the bidentate coordination mode. We discuss the relationship between the amino acid length of synthetic peptide analogues and the formation of Ca(2+)-bound coordination structure.
    Biopolymers 08/2006; 82(4):339-43. · 2.88 Impact Factor
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    ABSTRACT: The zona pellucida is the acellular transparent envelope surrounding the mammalian oocyte. An analysis of the changes in the structures of zona pellucida proteins is essential for understanding the molecular mechanisms underlying the important physiological roles of the zona during fertilization and preimplantation. The hardening of the zona caused by the structural changes during fertilization is generally accepted to be responsible for blocking polyspermy. In this study, we analyzed changes in the secondary structure of the zona during fertilization by Fourier transform infrared (FTIR) spectroscopy and transmission electron microscopy. The predominance of beta-sheet structure in porcine ovarian egg zona proteins in water was ascertained using FTIR spectra. Alpha-helix structure was also present. The attenuated total reflection (ATR)-FTIR spectrum of intact, unsolubilized porcine zonae pellucidae from ovarian eggs indicated that the zona proteins in the native zona pellucida also have beta-structure as the main constituent. Attenuated total reflection-FTIR spectroscopy of intact bovine zona pellucida obtained from ovarian and fertilized eggs at the blastocyst stage revealed that the beta-structure content increased during fertilization. Furthermore, a reduction of the thickness of the zona during fertilization was observed using transmission electron microscopy. Therefore, the change in the zona architecture that causes hardening of the zona during fertilization is accompanied by changes in the secondary structure of the zona proteins.
    Experimental Biology and Medicine 03/2006; 231(2):166-71. · 2.80 Impact Factor
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    ABSTRACT: Six missense mutations in human cardiac troponin I (cTnI) were recently found to cause restrictive cardiomyopathy (RCM). We have bacterially expressed and purified these human cTnI mutants and examined their functional and structural consequences. Inserting the human cTnI into skinned cardiac muscle fibers showed that these mutations had much greater Ca2+-sensitizing effects on force generation than the cTnI mutations in hypertrophic cardiomyopathy (HCM). The mutation K178E in the second actin-tropomyosin (Tm) binding region showed a particularly potent Ca2+-sensitizing effect among the six RCM-causing mutations. Circular dichroism and nuclear magnetic resonance spectroscopy revealed that this mutation does not extensively affect the structure of the whole cTnI molecule, but induces an unexpectedly subtle change in the structure of a region around the mutated residue. The results indicate that the K178E mutation has a localized effect on a structure that is critical to the regulatory function of the second actin-Tm binding region of cTnI. The present study also suggests that both HCM and RCM involving cTnI mutations share a common feature of increased Ca2+ sensitivity of cardiac myofilament, but more severe change in Ca2+ sensitivity is associated with the clinical phenotype of RCM.
    Biochemical and Biophysical Research Communications 01/2006; 338(3):1519-26. · 2.28 Impact Factor
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    ABSTRACT: Fourier-transform infrared spectroscopy (FT-IR) was applied to study the coordination structure of Ca2+ bound in Akazara scallop troponin C (TnC) and its site-directed mutant possessing inactivated Site IV (E142D mutant) in D2O solution. The COO− antisymmetric stretching region provides information about the coordination modes of a COO− group to a metal ion. The wild type exhibits a band at 1543cm−1 in the Ca2+-bound state, indicating that the side-chain COO− group of Glu142 (the position 12 of Site IV) serves as the ligand for Ca2+ in the bidentate coordination mode [F. Yumoto, M. Nara, H. Kagi, W. Iwasaki, T. Ojima, K. Nishita, K. Nagata, M. Tanokura, Eur. J. Biochem. 268 (2001) 6284–6290]. However, the E142D mutant showed no band around 1543cm−1 in the Ca2+-loaded state, indicating that the side-chain COO− group of Asp142 does not bind to Ca2+ in the bidentate coordination mode. This result suggests that the absence of a methylene group is critical for the Ca2+ coordination structure of Akazara scallop TnC. The Ca2+-ligand interaction at Site IV is discussed in comparison with the results of synthetic peptide analogues of Site IV of Akazara scallop TnC.
    Vibrational Spectroscopy - VIB SPECTROSC. 01/2006; 42(2):188-191.
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    ABSTRACT: Vertebrate troponin regulates muscle contraction through alternative binding of the C-terminal region of the inhibitory subunit, troponin-I (TnI), to actin or troponin-C (TnC) in a Ca(2+)-dependent manner. To elucidate the molecular mechanisms of this regulation by molluskan troponin, we compared the functional properties of the recombinant fragments of Akazara scallop TnI and rabbit fast skeletal TnI. The C-terminal fragment of Akazara scallop TnI (ATnI(232-292)), which contains the inhibitory region (residues 104-115 of rabbit TnI) and the regulatory TnC-binding site (residues 116-131), bound actin-tropomyosin and inhibited actomyosin-tropomyosin Mg-ATPase. However, it did not interact with TnC, even in the presence of Ca(2+). These results indicated that the mechanism involved in the alternative binding of this region was not observed in molluskan troponin. On the other hand, ATnI(130-252), which contains the structural TnC-binding site (residues 1-30 of rabbit TnI) and the inhibitory region, bound strongly to both actin and TnC. Moreover, the ternary complex consisting of this fragment, troponin-T, and TnC activated the ATPase in a Ca(2+)-dependent manner almost as effectively as intact Akazara scallop troponin. Therefore, Akazara scallop troponin regulates the contraction through the activating mechanisms that involve the region spanning from the structural TnC-binding site to the inhibitory region of TnI. Together with the observation that corresponding rabbit TnI-fragment (RTnI(1-116)) shows similar activating effects, these findings suggest the importance of the TnI N-terminal region not only for maintaining the structural integrity of troponin complex but also for Ca(2+)-dependent activation.
    FEBS Journal 10/2005; 272(17):4475-86. · 4.25 Impact Factor
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    ABSTRACT: ST0811 from Sulfolobus tokodaii strain 7, a member of the YjgF/YER057c/UK114 protein family, was crystallized by the sitting-drop vapour-diffusion method using PEG 10,000 as precipitant. The crystals diffracted X-rays to beyond 2.0 A resolution using an in-house rotating-anode generator. The crystals belonged to the rhombohedral space group R3, with hexagonal unit-cell parameters a = b = 55.0, c = 223.2 A. The crystals contained two molecules in the asymmetric unit (VM = 2.3 A3 Da(-1)) and had a solvent content of 47%.
    Acta Crystallographica Section F Structural Biology and Crystallization Communications 10/2005; 61(Pt 9):828-30. · 0.55 Impact Factor
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    ABSTRACT: Troponin and tropomyosin on actin filaments constitute a Ca2+-sensitive switch that regulates the contraction of vertebrate striated muscle through a series of conformational changes within the actin-based thin filament. Troponin consists of three subunits: an inhibitory subunit (TnI), a Ca2+-binding subunit (TnC), and a tropomyosin-binding subunit (TnT). Ca2+-binding to TnC is believed to weaken interactions between troponin and actin, and triggers a large conformational change of the troponin complex. However, the atomic details of the actin-binding sites of troponin have not been determined. Ternary troponin complexes have been reconstituted from recombinant chicken skeletal TnI, TnC, and TnT2 (the C-terminal region of TnT), among which only TnI was uniformly labelled with 15N and/or 13C. By applying NMR spectroscopy, the solution structures of a "mobile" actin-binding domain (approximately 6.1 kDa) in the troponin ternary complex (approximately 52 kDa) were determined. The mobile domain appears to tumble independently of the core domain of troponin. Ca2+-induced changes in the chemical shift and line shape suggested that its tumbling was more restricted at high Ca2+ concentrations. The atomic details of interactions between actin and the mobile domain of troponin were defined by docking the mobile domain into the cryo-electron microscopy (cryo-EM) density map of thin filament at low [Ca2+]. This allowed the determination of the 3D position of residue 133 of TnI, which has been an important landmark to incorporate the available information. This enabled unique docking of the entire globular head region of troponin into the thin filament cryo-EM map at a low Ca2+ concentration. The resultant atomic model suggests that troponin interacted electrostatically with actin and caused the shift of tropomyosin to achieve muscle relaxation. An important feature is that the coiled-coil region of troponin pushed tropomyosin at a low Ca2+ concentration. Moreover, the relationship between myosin and the mobile domain on actin filaments suggests that the latter works as a fail-safe latch.
    Journal of Molecular Biology 10/2005; 352(1):178-201. · 3.91 Impact Factor
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    ABSTRACT: Ca(2+)-binding sites I and II in the N-terminal lobe of molluscan troponin C (TnC) have lost the ability to bind Ca(2+) due to substitutions of the amino acid residues responsible for Ca(2+) liganding. To evaluate the functional importance of the Ca(2+)-deficient N-terminal lobe in the Ca(2+)-regulatory function of molluscan troponin, we constructed chimeric TnCs comprising the N-terminal lobes from rabbit fast muscle and squid mantle muscle TnCs and the C-terminal lobe from akazara scallop TnC, TnC(RA), and TnC(SA), respectively. We characterized their biochemical properties as compared with those of akazara scallop wild-type TnC (TnC(AA)). According to equilibrium dialysis using (45)Ca(2+), TnC(RA), and TnC(SA) bound stoichiometrically 3 mol Ca(2+)/mol and 1 mol Ca(2+)/mol, respectively, as expected from their primary structures. All the chimeric TnCs exhibited difference-UV-absorption spectra at around 280-290 nm upon Ca(2+) binding and formed stable complexes with akazara scallop troponin I, even in the presence of 6M urea, if Ca(2+) was present. However, when the troponin complexes were constructed from chimeric TnCs and akazara scallop troponin T and troponin I, they showed different Ca(2+)-regulation abilities from each other depending on the TnC species. Thus, the troponin containing TnC(SA) conferred as high a Ca(2+) sensitivity to Mg-ATPase activity of rabbit actomyosin-akazara scallop tropomyosin as did the troponin containing TnC(AA), whereas the troponin containing TnC(RA) conferred virtually no Ca(2+) sensitivity. Our findings indicate that the N-terminal lobe of molluscan TnC plays important roles in molluscan troponin regulation, despite its inability to bind Ca(2+).
    Archives of Biochemistry and Biophysics 05/2005; 436(1):83-90. · 3.37 Impact Factor
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    ABSTRACT: Six missense mutations in human cardiac troponin I (cTnI) were recently found to cause restrictive cardiomyopathy (RCM). We have bacterially expressed and purified these human cTnI mutants and examined their functional and structural consequences. Inserting the human cTnI into skinned cardiac muscle fibers showed that these mutations had much greater Ca{sup 2+}-sensitizing effects on force generation than the cTnI mutations in hypertrophic cardiomyopathy (HCM). The mutation K178E in the second actin-tropomyosin (Tm) binding region showed a particularly potent Ca{sup 2+}-sensitizing effect among the six RCM-causing mutations. Circular dichroism and nuclear magnetic resonance spectroscopy revealed that this mutation does not extensively affect the structure of the whole cTnI molecule, but induces an unexpectedly subtle change in the structure of a region around the mutated residue. The results indicate that the K178E mutation has a localized effect on a structure that is critical to the regulatory function of the second actin-Tm binding region of cTnI. The present study also suggests that both HCM and RCM involving cTnI mutations share a common feature of increased Ca{sup 2+} sensitivity of cardiac myofilament, but more severe change in Ca{sup 2+} sensitivity is associated with the clinical phenotype of RCM.
    Biochemical and Biophysical Research Communications - BIOCHEM BIOPHYS RES COMMUN. 01/2005;
  • Journal of Biomolecular NMR 10/2004; 30(1):109-10. · 2.85 Impact Factor

Publication Stats

440 Citations
85.79 Total Impact Points

Institutions

  • 2001–2012
    • The University of Tokyo
      • Department of Applied Biological Chemistry
      Tokyo, Tokyo-to, Japan
  • 2006–2008
    • Tokyo Medical and Dental University
      • College of Liberal Arts and Sciences
      Edo, Tōkyō, Japan
  • 2005–2007
    • The Jikei University School of Medicine
      • Laboratory of Neurophysiology
      Edo, Tōkyō, Japan