Calcium binding induces conformational changes in muscle regulatory proteins

Silva, Ana Claudia R. da; Reinach, Fernando C.

doi:10.1016/0968-0004(91)90024-p

Cited by 110 publications

(52 citation statements)

References 25 publications

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“…The fact that the three troponin subunits can refold and reassociate in vitro (Greaser & Gergely, 1971) has allowed the use of troponin subunits produced in Escherichia coli to study the molecular mechanism of this regulatory complex. Expression of TnC in bacteria (Chen et al, 1988;Reinach & Karlsson, 1988;Xu & HitchcockDeGregori, 1988) and the analysis of site-directed mutants (Fujimori et al, 1990;Grabarek et al, 1990;Putkey et al, 1991;Sheng et a]., 1991;Negele et al, 1992;Pearlstone et al, 1992;Silva et al, 1993) in conjunction with the determination of the crystal structure of TnC (Herzberg & James, 1985;Sundarlingam et al, 1985) has provided a better understanding of the calcium-induced conformational change in TnC (Silva & Reinach, 1991;Grabarek et al, 1992). This conformational change is responsible for the modulation of the inhibitory action of Tnl.…”

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Cloning and expression of chicken skeletal muscle troponin I in Escherichia coli: The role of rare codons on the expression level

et al. 1993

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Cloning and expression of chicken skeletal muscle troponin I in Escherichia coli: The role of rare codons on the expression level

et al. 1993

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“…Five active sites have been characterized, a phosphorylation site on serine 15 in exon 2 and 4 EF-hand domains, one of which has retained the ability to bind a metal ion and which is most likely occupied by Mg 2ϩ in vivo. 69 Five mutations were reported ( Figure 3) 63,68 : 2 of them (E22K and A13T) are associated with the same rare phenotype seen with mutations in MYL3 (see above) involving mid left ventricular chamber thickening, 63 whereas mutations F18L and R58Q are associated with familial and classical forms of hypertrophic cardiomyopathy.…”

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Familial Hypertrophic Cardiomyopathy

Bonne

Carrier

Richard

et al. 1998

Circulation Research

314

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Abstract-Hypertrophic cardiomyopathy is characterized by left and/or right ventricular hypertrophy, which is usually asymmetric and involves the interventricular septum. Typical morphological changes include myocyte hypertrophy and disarray surrounding the areas of increased loose connective tissue. Arrhythmias and premature sudden deaths are common. Hypertrophic cardiomyopathy is familial in the majority of cases and is transmitted as an autosomal-dominant trait. The results of molecular genetics studies have shown that familial hypertrophic cardiomyopathy is a disease of the sarcomere involving mutations in 7 different genes encoding proteins of the myofibrillar apparatus: ␤-myosin heavy chain, ventricular myosin essential light chain, ventricular myosin regulatory light chain, cardiac troponin T, cardiac troponin I, ␣-tropomyosin, and cardiac myosin binding protein C. In addition to this locus heterogeneity, there is a wide allelic heterogeneity, since numerous mutations have been found in all these genes. The recent development of animal models and of in vitro analyses have allowed a better understanding of the pathophysiological mechanisms associated with familial hypertrophic cardiomyopathy. One can thus tentatively draw the following cascade of events: The mutation leads to a poison polypeptide that would be incorporated into the sarcomere. This would alter the sarcomeric function that would result (1) in an altered cardiac function and then (2) in the alteration of the sarcomeric and myocyte structure. Some mutations induce functional impairment and support the pathogenesis hypothesis of a "hypocontractile" state followed by compensatory hypertrophy. Other mutations induce cardiac hyperfunction and determine a "hypercontractile" state that would directly induce cardiac hypertrophy. The development of other animal models and of other mechanistic studies linking the genetic mutation to functional defects are now key issues in understanding how alterations in the basic contractile unit of the cardiomyocyte alter the phenotype and the function of the heart. (Circ Res. 1998;83:580-593.)

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“…Together with actin and tropomyosin, troponin regulates muscle contraction (Zot and Potter, 1987). Calcium binding to troponin C induces a conformational change which counteracts the inhibitory action of troponin I (Silva and Reinach, 1991). The third component, troponin T binds tropomyosin and is probably involved in transmitting this conformational change to tropomyosin and actin.…”

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Assembly of functional skeletal muscle troponin complex in Escherichia coli

Malnic

Reinach

1994

European Journal of Biochemistry

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The production of multi-subunit proteins of eukaryotic origin in Escherichia coli usually relies on the different subunits being expressed individually and the protein being reassembled in vitro. Here we describe the construction and characterization of plasmids capable of coexpressing the three subunits of chicken skeletal muscle troponin complex in E. coli. We demonstrate that the troponin subunits assembled in the cytoplasm of E. coli cell are fully functional. The troponin complex was purified to homogeneity in high yields. When reconstituted into actin filaments, the complex assembled in vivo was capable of regulating the myosin ATPase with a calcium dependence that was identical to the complex reconstituted in vitro. These results demonstrate that the coexpression of the subunits of a protein complex can prevent the accumulation of denatured proteins in inclusion granules.

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Calcium binding induces conformational changes in muscle regulatory proteins

Cited by 110 publications

References 25 publications

Cloning and expression of chicken skeletal muscle troponin I in Escherichia coli: The role of rare codons on the expression level

Cloning and expression of chicken skeletal muscle troponin I in Escherichia coli: The role of rare codons on the expression level

Familial Hypertrophic Cardiomyopathy

Assembly of functional skeletal muscle troponin complex in Escherichia coli

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