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How do regulated thin filaments with hypertrophic cardiomyopathy-linked α-cardiac actin affect actomyosin interactions?

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Title: How do regulated thin filaments with hypertrophic cardiomyopathy-linked α-cardiac actin affect actomyosin interactions?
Author: Liu, Haidun
Department: Department of Molecular and Cellular Biology
Program: Molecular and Cellular Biology
Advisor: Dawson, John
Abstract: Hypertrophic cardiomyopathy (HCM) is a heart disease associated with substitution mutations of sarcomeric proteins. This thesis describes investigations of the effects of mutations in α-cardiac actin (ACTC) subdomain 1 (E99K, R95C, F90Δ, and H88Y) on actomyosin interactions. ACTC proteins were expressed in a Sf21/baculovirus system and used in biochemical and biophysical assays to calculate the duty ratio (r). Compared to human ACTC (WTrec), E99K, R95C, F90Δ, and H88Y yielded higher, lower, or similar r. The varying r suggested that actomyosin changes may occur at the level of regulation by troponin and tropomyosin. Compared to WTrec regulated thin filaments (RTFs), R95C RTFs yielded no changes in r and E99K RTF yielded a decreased r, suggesting that the binding of myosin to actin may not be altered. However, E99K and R95C RTFs showed lower sensitivity to calcium, suggesting the altered cross-bridge cycling rate might lead to HCM.
URI: http://hdl.handle.net/10214/10224
Date: 2017-01


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