Structural and Functional Analysis of Troponins from Scallop Striated and Human Cardiac Muscles
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, 4, 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, 7, 8, 9, 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.
KeywordsATPase Activity Cardiac Troponin Regulatory Light Chain K178E Mutation Restrictive Cardiomyopathy
Unable to display preview. Download preview PDF.
- 8.C. S. Farah, and F. C. Reinach, The troponin complex and regulation of muscle contraction. FASEB, J. 9, 755–767 (1995).Google Scholar
- 33.F. Takahashi-Yanaga, S. Morimoto, K. Harada, R. Minakami, F. Shiraishi, M. Ohta, Q.-W. Lu, T. Sasaguri, and I. Ohtsuki, Functional consequences of the mutations in human cardiac troponin I gene found in familial hypertrophic cardiomyopathy, J. Mol. Cell. Cardiol. 3, 2095–2107 (2001).CrossRefGoogle Scholar
- 38.S. Morimoto, Q.-W. Lu, K. Harada, F. Takahashi-Yanaga, R. Minakami, M. Ohta, T. Sasaguri, and I. Ohtsuki, Ca2+-desensitizing effect of a deletion mutation ΔK210 in cardiac troponin T that causes familial dilated cardiomyopathy, Proc. Natl. Acad. Sci. USA 99, 913–918 (2002).PubMedCrossRefGoogle Scholar
- 43.AJ842179 NCBI, Bos taurus tnni3 gene for cardiac troponin I, exons 1–8.Google Scholar
- 47.C. Seidman et al., CardioGenomics, Mutation Database, Cardiac troponin I URL: http://genetics.med.harvard.edu/~seidman/cg3/muts/TNNI3_mutations_TOC.html.Google Scholar
- 50.F. Yumoto, Q. W. Lu, S. Morimoto, H. Tanaka, N. Kono, K. Nagata, T. Ojima, F. Takahashi-Yanaga, Y. Miwa, T. Sasaguri, K. Nishita, M. Tanokura, I. Ohtsuki. Drastic Ca2+ sensitization of myofilament associated with a small structural change in troponin I in inherited restrictive cardiomyopathy, Biochem. Biophys. Res. Commun. 338, 1519–1526 (2005).PubMedCrossRefGoogle Scholar
- 51.S. Morimoto, and I. Ohtsuki, Ca2+-and Sr2+-sensitivity of the ATPase activity of rabbit skeletal muscle myofibrils: effect of the complete substitution of troponin C with cardiac troponin C, calmodulin, and parvalbumins, J. Biochem. 101, 230–291 (1987).Google Scholar