From the Crystal Structure of Troponin to the Mechanism of Calcium Regulation of Muscle Contraction
In 2003, we published the crystal structures of the core domains of human cardiac muscle troponin (Takeda et al., 2003). Thus, for the first time we were able to visualize the architecture of the molecule; and to see how the three components (TnC, TnI and TnT) fold together to form the troponin molecule. Moreover, our molecular switch mechanism was confirmed, which was previously proposed (Vassylyev et al., 1998) based on the crystal structure of a much smaller complex (the full length TnC in complex with TnI (1–47), a short N-terminal fragment of TnI, both from rabbit skeletal muscle troponin). Namely, a C-terminal TnI segment (117–126 in the rabbit skeletal troponin sequence), directly downstream from the “inhibitory region” (104–115), forms an amphipathic α-helix and interacts with the hydrophobic pocket of the TnC N-lobe in a [Ca2+]-dependent manner. This binding removes the inhi-bitory region from actin-tropomyosin, and thereby relieves the inhibitory action of TnI.
KeywordsElementary Mechanism Inhibitory Region Rabbit Skeletal Muscle Ribbon Model Side Chain Volume
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