TROPOMYOSIN LENGTH AND 2-STRANDED F-ACTIN FLEXIBILITY IN THE THIN FILAMENT

In muscle thin filaments, each tropomyosin molecule is considered to be a rope-like structure that winds along the filament in contact with seven consecutive actin monomers on the same strand of the two-stranded actin helix. Taking into account the head-to-tail overlap of the tropomyosin molecule, the effective length of this ''rope'' is about 405 Angstrom, which is believed to be conserved. Tropomyosin appears to be neither extensible nor compressible in its axial direction, although it may possess much flexibility in the transverse direction. During the ''maximally on'' state, characterized by the presence of Ca2+ and the strong binding between actin and myosin subfragment 1, the following conditions are thought to occur: the motion and associated flexibility of tropomyosin are reduced; the actin filament flexibility increases; a maximum number of equivalent tropomyosin binding sites on actin are concurrently saturated; and the tropomyosin molecule maintains an average thin filament radius of 38 to 40 Angstrom. Under these potentiated conditions, the length of tropomyosin can be used to determine the limits on the underlying ''cumulative angular disorder'' of the actin filament with which it interacts. Our calculations show that only a small amount (similar to 1 to 3 degrees) of this type of actin monomer rotational disorder is possible at this stage of the contractile cycle, unless the length of the tropomyosin molecule is increased substantially between the head-to-tail joints. However, if the dominant type of F-actin rotational flexibility is between two relatively rigid actin strands (the lateral slipping/rotational offset model), all of the above actin-tropomyosin interactions can be completely and easily accommodated. We also discuss the implications of an interdomain hinge in G-actin and the possibility that there may be fewer than seven equivalent sites on actin that are saturated by tropomyosin concurrent.