Tropomyosin exon 6b is troponin-specific and required for correct acto-myosin regulation

Maytum, Robin and Bathe, Friederike and Konrad, Manfred and Geeves, Michael A. (2004) Tropomyosin exon 6b is troponin-specific and required for correct acto-myosin regulation. Journal of Biological Chemistry, 279 (18). pp. 18203-9. ISSN 0021-9258. (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

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The specificity of tropomyosin (Tm) exon 6b for interaction with and functioning of troponin (Tn) has been studied using recombinant fibroblast Tm isoforms 5a and 5b. These isoforms differ internally by exons 6a/6b and possess non-muscle exons 1b/9d at the termini, hence they lack the primary TnT(1)-tropomyosin interaction, allowing study of exon 6 exchange in isolation from this. Using kinetic techniques to measure regulation of myosin S1 binding to actin and fluorescently labeled Tm to directly measure Tn binding, we show that binding of Tn to both isoforms is similar (0.1-0.5 microm) and both produce well regulated systems. Calcium has little effect on Tn binding to the actin.Tm complex and both exons produce a 3-fold reduction in the S1 binding rate to actin.Tm.Tn in its absence. This confirms previous results that show exon 6 has little influence on Tn affinity to actin.Tm or its ability to fully inhibit the acto-myosin interaction. Thin filaments reconstituted with Tn and Tm5a or skeletal Tm (containing exon 6b) show nearly identical calcium dependence of acto-myosin regulation. However, Tm5b produces a dramatic increase in calcium sensitivity, shifting the activation mid-point by almost an order of magnitude. This shows that exon 6 sequence and, hence, Tm structure in this region have a significant effect upon the calcium regulation of Tn. This finding supports evidence that familial hypertrophic cardiomyopathy mutations occurring adjacent to this region can effect calcium regulation.

Item Type: Article
Additional information: 0021-9258 (Print) Journal Article
Uncontrolled keywords: Actomyosin/*metabolism Animals Calcium/pharmacology Cardiomyopathy, Hypertrophic, Familial/genetics Exons/*physiology Humans Kinetics Muscle, Skeletal Myosin Subfragments/metabolism Protein Binding/genetics Protein Isoforms/genetics/metabolism/physiology Rabbits Research Support, Non-U.S. Gov't Substrate Specificity Tropomyosin/*genetics/metabolism/physiology Troponin/*metabolism
Subjects: Q Science
Divisions: Faculties > Science Technology and Medical Studies > School of Biosciences
Depositing User: Michael Geeves
Date Deposited: 29 May 2009 06:13
Last Modified: 29 Apr 2014 08:19
Resource URI: (The current URI for this page, for reference purposes)
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