The structural transition in troponin C induced by the binding of two calcium
ions involves an "opening" of the structure, an event that triggers skeletal
muscle contraction. We have solved the solution structure of a mutant (E41A) of
the regulatory domain of skeletal troponin C wherein one bidentate ligand to the
calcium in site I is missing. This structure remains "closed" upon calcium
binding, indicating that the linkage between calcium binding and the induced
conformational change has been broken. This provides a snapshot of skeletal
troponin C between the off and on state and thereby valuable insight into the
mechanism of regulation within skeletal TnC. Although several factors contribute
to the triggering mechanism, the opening of the troponin C structure is
ultimately dependent on one amino acid, Glu41. Insights into the structure of
cardiac troponin C can also be derived from this skeletal mutant.
