THE TROPONIN COMPLEX AND REGULATION OF MUSCLE-CONTRACTION

In a wide variety of cellular settings, from organelle transport to mu scle contraction, Ca2+ binding to members of the EF hand family of pro teins controls the interaction between actin and different myosins tha t are responsible for generating movement. In vertebrate skeletal and cardiac muscle the Ca2+-binding protein troponin C (TnC) is one subuni t of the ternary troponin complex which, through its association with actin and tropomyosin on the thin filament, inhibits the actomyosin in teraction at sub2+ micromolar Ca2+ concentrations and stimulates the i nteraction at micromolar Ca2+ concentrations. Because TnC does not int eract directly with actin or tropomyosin, the Ca2+-binding signal must be transmitted to the thin filament via the other two troponin subuni ts: troponin I (TnI), the inhibitory subunit, and troponin T (TnT), th e tropomyosin-binding subunit. Thus, the troponin complex is a Ca2+-se nsitive molecular switch and the structures of and interactions betwee n its components have been of great interest for many years. Although the crystal structure of TnC has been known for almost a decade, the m olecular structures of TnI and TnT are not known and therefore convinc ing models of the organization of the troponin complex and the Ca2+-in duced changes in its structure have not been forthcoming. Recent advan ces on a wide variety of fronts including 1) the bacterial expression and characterization of mutants of TnC, TnI, and TnT; 2) cross-linking and fluorescence studies; and 3) the determination of the crystal and nuclear magnetic resonance structures of synthetic and recombinant tr oponin fragments and complexes between EF hand proteins and their targ et peptides have provided new insights into the nature of the interact ions between troponin subunits. This review discusses these recent adv ances with the aim of critically assessing molecular models of the nat ure of the Ca2+-induced structural transition in troponin.