Abstract
Contraction of skeletal muscle is regulated by Ca2+ binding to troponin C which interrupts troponin I binding to actin. Troponin T links troponin I to tropomyosin and moves tropomyosin away from its inhibitory position on actin. Troponin T may also play a direct regulatory role. The C-terminal 14 residues of cardiac troponin T are required for full inhibition at low Ca2+. Those residues also limit the activation at high Ca2+ (Baxley et al., 2017, Biochemistry). Because of significant differences between the cardiac and skeletal troponin, it is unclear if troponin T has a similar function in skeletal muscle regulation. We prepared human skeletal troponin in which troponin T has the C-terminal 16 residues truncated. We also prepared troponin in which the basic residues within the last 16 residues of troponin T have been replaced by Ala (skeletal HAHA troponin T). Among the changes noted are an almost 5-fold increase in the ATPase activity at high Ca2+ for the HAHA troponin T and a shift of the force-pCa curve to lower Ca2+ by a full Log unit. Therefore, the C-terminal region of skeletal troponin T has a very large impact on skeletal regulation in both solution and in skinned psoas fibers, larger than reported with cardiac troponin. The basic residues in the C-terminal region of troponin T form an essential regulatory element of skeletal muscle. ALD and LZ contributed equally to this work.
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