Mechanisms of the myosin converter

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Newhard, Christopher Stewart
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Electronic thesis
Biochemistry and biophysics
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To test this hypothesis, we utilized the unique properties of the Drosophila jump muscle system which enables both genetic modification of the converter and the measurement of the muscle FVR. In Drosophila, there are five endogenous versions of the converter (11a, 11b, 11c, 11d, and 11e) that are expressed in different muscle types. We evaluated five transgenic fly lines each expressing only one of the converters in their jump muscles. The converter expressed had a large influence on FVR curvature (i.e. load sensitivity) and maximum shortening velocity. Converter 11a, normally found in the indirect flight muscle, had the highest degree of FVR curvature and the fastest maximum shortening velocity of the five transgenic converter lines. In contrast, converter 11d, found in larvae body wall muscle, had the most linear FVR and slowest maximum shortening velocity. These changes in the FVR enabled maximum power to be generated at different shortening velocities. The changes in FVR curvature suggest modulation of cross-bridge attachment of detachment rates when related to A. F. Huxley’s 1957 model. To investigate a structural mechanism behind these changes in the FVR, we constructed five myosin S-1 homology models. Hydrogen bond motifs and hydropathy differentiated the five converters. We propose that the converter’s stiffness, specifically of the mobility of the central alpha helix and lower strand, is at least part of the mechanism behind myosin load dependent properties.
The hyperbolic shape of the muscle force-velocity relationship (FVR) is characteristic of all muscle fiber types. This shape has been proposed to be set by load-dependent properties of myosin isoforms. However, the structural elements in myosin that determine such load-dependence are unresolved. We hypothesized that the myosin converter is critical for setting load-dependent myosin properties that vary between muscle fiber types.
May 2018
School of Science
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Rensselaer Polytechnic Institute, Troy, NY
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