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FIGURE 17.29 • A drawing of the thick and thin filaments of skeletal muscle in cross-section showing the changes that are postulated to occur when Ca2+ binds to troponin C.

monomers. However, the binding of Ca2+ ions to troponin C appears to increase the binding of troponin C to troponin I, simultaneously decreasing the interaction of troponin I with actin. As a result, tropomyosin slides deeper into the actin-thin filament groove, exposing myosin-binding sites on actin, and initiating the muscle contraction cycle (Figure 17.23). Because the troponin complexes can interact only with every seventh actin in the thin filament, the conformational changes that expose myosin-binding sites on actin may well be cooperative. Binding of an S1 head to an actin may displace tropomyosin and the troponin complex from myosin-binding sites on adjacent actin subunits.

The Interaction of Ca2+ with Troponin C

There are four Ca2+-binding sites on troponin C—two high-affinity sites on the carboxy-terminal end of the molecule, labeled III and IV in Figure 17.30, and two low-affinity sites on the amino-terminal end, labeled I and II. Ca2+ binding to sites III and IV is sufficiently strong (KD = 0.1 ¡M) that these sites are presumed to be filled under resting conditions. Sites I and II, however, where the KD is approximately 10 ¡ M, are empty in resting muscle. The rise of Ca2+ levels when contraction is signaled leads to the filling of sites I and II, causing a conformation change in the amino-terminal domain of TnC. This conformational change apparently facilitates a more intimate binding of TnI to TnC that involves the C helix, and also possibly the E helix of TnC. The increased interaction between TnI and TnC results in a decreased interaction between TnI and actin.

FIGURE 17.30 • (a) A ribbon diagram and (b) a molecular graphic showing two slightly different views of the structure of troponin C. Note the long a-helical domain connecting the N-terminal and C-terminal lobes of the molecule.

FIGURE 17.30 • (a) A ribbon diagram and (b) a molecular graphic showing two slightly different views of the structure of troponin C. Note the long a-helical domain connecting the N-terminal and C-terminal lobes of the molecule.

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