Contemporary Reviews in Cardiovascular Medicine Cardiac Titin A Multifunctional

Titin constitutes the third myofilament of cardiac muscle,with a single giant polypeptide spanning from the Z disk to the M-band region of the sarcomere1 (Figure 1). The 1.0-MDa region in the I band is extensible and consists of tandemly arranged immunoglobulin-like domains that make up proximal (near the Z disk) and distal (near the A-I junction) segments, interspersed by the PEVK sequence (rich in proline, glutamate, valine, and lysine residues) and the N2B element.2 Each functions as a distinct spring element.3 The C-terminal 2 MDa of titin is located in the A band and is inextensible. It is composed of regular arrays of immuno-globulin and fibronectin type 3 modules that form so-called super-repeats.2 A-band titin may function as a molecular ruler, regulating assembly of the thick filament.2,4,5 The 250-kDa COOH-terminal region of titin is an integral part of the M band and contains a kinase domain.6,7 As in the