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Author ORCID Identifier
https://orcid.org/0000-0001-5608-0562
AccessType
Open Access Dissertation
Document Type
dissertation
Degree Name
Doctor of Philosophy (PhD)
Degree Program
Kinesiology
Year Degree Awarded
2022
Month Degree Awarded
September
First Advisor
Edward Debold
Second Advisor
Jay Gump
Third Advisor
Dhandapani Venkataraman
Subject Categories
Amino Acids, Peptides, and Proteins | Biochemistry | Biological Phenomena, Cell Phenomena, and Immunity | Biophysics | Cellular and Molecular Physiology | Molecular Biology | Nanomedicine | Other Chemicals and Drugs | Other Kinesiology
Abstract
Molecular motors, such as myosin, have evolved to transduce chemical energy from ATP into mechanical work to drive essential cellular processes, from muscle contraction to vesicular transport. Dysfunction in these motors is a root cause of many pathologies necessitating the application of intrinsic control over molecular motor function. We hypothesized that altering the myosin’s energy substrate via minor positional changes to the triphosphate portion of the molecule will allow us to control the protein and affect its in vitro function. We utilized positional isomers of a synthetic non-nucleoside triphosphate, azobenzene triphosphate, and assessed whether myosin’s force- and motion-generating capacity could be controlled at both the ensemble and single-molecule levels. This successfully demonstrated the ability to alter a substrate to exert intrinsic control over a protein’s function by affecting distinct steps in myosin’s chemomechanical cycle. A deeper investigation of the mechanisms underlying any enhancement or inhibition of myosin’s function may reveal potential avenues for novel approaches to treat certain myopathies.
DOI
https://doi.org/10.7275/30257835
Recommended Citation
Woodward, Mike K., "Controlling Myosin’s Function via Interactions between the Substrate and the Active Site" (2022). Doctoral Dissertations. 2692.
https://doi.org/10.7275/30257835
https://scholarworks.umass.edu/dissertations_2/2692
Included in
Amino Acids, Peptides, and Proteins Commons, Biochemistry Commons, Biological Phenomena, Cell Phenomena, and Immunity Commons, Biophysics Commons, Cellular and Molecular Physiology Commons, Molecular Biology Commons, Nanomedicine Commons, Other Chemicals and Drugs Commons, Other Kinesiology Commons