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    Defining the Role of the C-Terminal Region of Troponin T by Analysis of a Series of Truncation Mutants

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    Author
    Johnson, Dylan James
    Abstract
    Familial hypertrophic cardiomyopathy and other cardiovascular diseases result from mutations of any of the contractile proteins. Mutations within the actin binding regulatory complex of proteins, including tropomyosin (Tm) and the three subunits of the troponin (Tn) complex (TnI, TnC, and TnT), change the operation of the Ca2+ dependent 3-way switch that controls movement. The Δ14-TnT mutation, which is missing the last 14 residues of its C-terminus, is particularly important as it leads to hypertrophic cardiomyopathy and early sudden death. Our laboratory found that incorporation of Δ14-TnT into the regulatory complex stabilizes the open (M) state and removes the blocked (B) state from the actin state distribution. This suggests the last fourteen residues of the C-terminus of TnT are essential in maintaining the open state and the blocked state of the thin filament. This function had not previously been attributed to TnT. Our lab aims to identify the key residues of TnT that are responsible for normal state distribution. This information will allow us to identify possible mechanisms of action of TnT and would facilitate the design of treatments of myopathies. We prepared truncation mutants of TnT that included Δ4, Δ6, Δ8, Δ10 and Δ14. We utilized two stopped flow kinetic assays and an ATPase assay to determine the effect of these deletions on the state distributions. Each assay supported the idea that successive deletions resulted in further diminished function. We conclude that all of the fourteen residues of the TnT C-terminus contribute to a similar extent to the function.
    URI
    http://hdl.handle.net/10342/5931
    Subject
     troponin; cardiomyopathy; TnT 
    Date
    2016-07-21
    Citation:
    APA:
    Johnson, Dylan James. (July 2016). Defining the Role of the C-Terminal Region of Troponin T by Analysis of a Series of Truncation Mutants (Master's Thesis, East Carolina University). Retrieved from the Scholarship. (http://hdl.handle.net/10342/5931.)

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    MLA:
    Johnson, Dylan James. Defining the Role of the C-Terminal Region of Troponin T by Analysis of a Series of Truncation Mutants. Master's Thesis. East Carolina University, July 2016. The Scholarship. http://hdl.handle.net/10342/5931. May 19, 2022.
    Chicago:
    Johnson, Dylan James, “Defining the Role of the C-Terminal Region of Troponin T by Analysis of a Series of Truncation Mutants” (Master's Thesis., East Carolina University, July 2016).
    AMA:
    Johnson, Dylan James. Defining the Role of the C-Terminal Region of Troponin T by Analysis of a Series of Truncation Mutants [Master's Thesis]. Greenville, NC: East Carolina University; July 2016.
    Collections
    • Chemistry
    • Master's Theses
    Publisher
    East Carolina University

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