Effects of the cardiomyopathy-causing E244D mutation of troponin T on the structures of cardiac thin filaments studied by small-angle X-ray scattering |
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Authors: | Tatsuhito Matsuo Fumiaki Kono Satoru Fujiwara |
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Affiliation: | Quantum Beam Science Research Directorate, National Institutes for Quantum and Radiological Science and Technology, 2-4 Shirakata, Tokai, Naka-Gun, Ibaraki 319-1106, Japan |
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Abstract: | Small-angle X-ray scattering experiments were carried out to investigate the structural changes of cardiac thin filaments induced by the cardiomyopathy-causing E244D mutation in troponin T (TnT). We examined native thin filaments (NTF) from a bovine heart, reconstituted thin filaments containing human cardiac wild-type Tn (WTF), and filaments containing the E244D mutant of Tn (DTF), in the absence and presence of Ca2+. Analysis by model calculation showed that upon Ca2+-activation, tropomyosin (Tm) and Tn in the WTF and NTF moved together in a direction to expose myosin-binding sites on actin. On the other hand, Tm and Tn of the DTF moved in the opposite directions to each other upon Ca2+-activation. These movements caused Tm to expose more myosin-binding sites on actin than the WTF, suggesting that the affinity of myosin for actin is higher for the DTF. Thus, the mutation-induced structural changes in thin filaments would increase the number of myosin molecules bound to actin compared with the WTF, resulting in the force enhancement observed for the E244D mutation. |
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Keywords: | SAXS small-angle X-ray scattering Tm tropomyosin Tn troponin Tn-CD troponin core domain NTF native thin filaments purified from a bovine heart WTF reconstituted thin filaments containing human cardiac wild-type Tn DTF reconstituted thin filaments containing human cardiac Tn with the E244D mutant of TnT Cardiac thin filament Cardiomyopathy Troponin Small-angle X-ray scattering |
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