Ca2+-regulated structural changes in troponin

Troponin senses Ca2+ to regulate contraction in striated muscle. Structures of skeletal muscle troponin composed of TnC (the sensor), Tnl (the regulator), and TnT (the link to the muscle thin filament) have been determined. The structure of troponin in the Ca2+-activated state features a nearly twofold symmetrical assembly of Tnl and TnT subunits penetrated asymmetrically by the dumbbell-shaped TnC subunit. Ca ions are thought to regulate contraction by controlling the presentation to and withdrawal of the Tnl inhibitory segment from the thin filament. Here, we show that the rigid central helix of the sensor binds the inhibitory segment of Tril in the Ca2+-activated state. Comparison of crystal structures of troponin in the Ca2+-activated state at 3.0 angstrom resolution and in the Ca2+-free state at 7.0 angstrom resolution shows that the long framework helices of Tnl and TnT, presumed to be a Ca2+- independent structural domain of troponin are unchanged. Loss of Ca ions causes the rigid central helix of the sensor to collapse and to release the inhibitory segment of Tnl. The inhibitory segment of Trill changes conformation from an extended loop in the presence of Ca2+ to a short alpha-helix in its absence. We also show that Anapoe, a detergent molecule, increases the contractile force of muscle fibers and binds specifically, together with the Tnl switch helix, in a hydrophobic pocket of TnC upon activation by Ca ions.