The Scaffolding Proteins Give Stability and Elasticity to the Sarcomere

Titin (also called connectin) is a giant molecule (~3×106 mw) associated with the thick filaments. The C terminus of titin is at the M-line. Between the M-line and the edges of the A-band titin lies over the surface of the thick filament. Titin continues free along the I-band and attaches to the Z-band, probably interacting both with actin and with alpha-actinin at its N terminus. At least six titin molecules are associated with the thick filament, three on either side of the M-line. Along the thick filament, titin may act as a molecular ruler. Within the A-band the molecule has 11 identical copies of repeats containing immunoglobulin and fibronectin sequences. These presumably align with the 11 bands along which C and H proteins are located.

The I-band region of titin is stretchable and is responsible for elasticity of the resting muscle, that is for the increase in resting tension with stretches above a certain length. It is debated whether the PEVK region of the molecule, a stretch containing prevalently Pro (P), Glu (E), Val (V), and Lys (K) residues, is responsible for the elasticity. In favor of this hypothesis, the PEVK region of titin in cardiac muscle (which is quite stiff) is shorter than that in skeletal muscle (which is more easily stretchable).

A result of titin’s elasticity within the I-band is that titin keeps the A-band centered in the sarcomere during contraction and/or stretching of the muscle (75). Nebulin is a second scaffolding protein. It is located along the filament and since its length varies in parallel to that of the thin filaments in different fibers, it is thought that nebulin may act as a ruler to determine thin filament length.