[46] molecular structure of troponin C and its implications for the Ca2+ triggering of muscle contraction

Publisher Summary This chapter explores what is known about Troponin C (TnC) from crystallographic studies and reviews how this information can be exploited to understand the nature of the conformational transition that the molecule undergoes upon Ca 2+ binding. TnC belongs to a class of intracellular proteins that are functionally dependent upon Ca 2+ concentration. It plays a key role in the regulation of muscle contraction as part of the regulatory complex troponin. This complex is formed from three protein molecules: troponin T (TnT), which binds to the tropomyosin of the thin filament; troponin I (TnI), which is the subunit that inhibits the Mg 2+ -activated ATPase of actomyosin; and TnC, the subunit which can bind a total of four Ca 2+ ions, two with high affinity (Ka≈10 7 M -1 ) to the C-terminal domain of the molecule and the other two with low affinity (Ka≈10 5 M -1 ) to the N terminal domain. It is the binding of Ca 2+ to the low-affinity binding sites (Ca 2+ -specific sites) that triggers muscle contraction, whereas the high affinity sites (Ca 2+ /Mg 2+ sites) are always occupied by metal ions under physiological conditions. Therefore, the N-terminal domain is considered the regulatory domain of TnC. Ca 2+ binding to this domain is associated with conformational changes to TnC that are transferred to other components of the muscle system, leading to the activation of muscle.