Abstract
Muscles are usually activated by calcium binding to the calcium sensory protein troponin-C, which is one of the three components of the troponin complex. However, in cardiac and insect flight muscle activation is also produced by mechanical stress. Little is known about the molecular bases of this calcium-independent activation. In Lethocerus, a giant water bug often used as a model system because of its large muscle fibers, there are two troponin-C isoforms, called F1 and F2, that have distinct roles in activating the muscle. It has been suggested that this can be explained either by differences in structural features or by differences in the interactions with other proteins. Here we have compared the structural and dynamic properties of the two proteins and shown how they differ. We have also mapped the interactions of the F2 isoform with peptides spanning the sequence of its natural partner, troponin-I. Our data have allowed us to build a model of the troponin complex and may eventually help in understanding the specialized function of the F1 and F2 isoforms and the molecular mechanism of stretch activation.
Highlights
Mechanical stress is an important element in cellular processes as different as muscle contraction, external mechanical loading, cell migration, and protein aggregation and misfolding
The interaction of myosin with actin is controlled by tropomyosin (Tm)2 and troponin (Tn), which are periodically arranged along the thin filaments [2, 3]
Mechanical measurements with Lethocerus indirect flight muscle (IFM) fibers in which TnC isoforms were exchanged suggest that F1TnC is important for stretch activation, whereas F2TnC is required for calcium-activated isometric tension [14, 20]
Summary
Our data have allowed us to build a model of the troponin complex and may eventually help in understanding the specialized function of the F1 and F2 isoforms and the molecular mechanism of stretch activation. Mechanical measurements with Lethocerus IFM fibers in which TnC isoforms were exchanged suggest that F1TnC is important for stretch activation, whereas F2TnC is required for calcium-activated isometric tension [14, 20]. This difference in properties was suggested to be due to structural differences or to formation of different interactions with other proteins [20]. The two isoforms have a similar structure, they have distinct dynamic behavior in solution, which may have profound consequences on how the two isoforms function and on their mechanical properties
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