Titin folding energy and elasticity

Abstract

Molecules of the giant protein titin are responsible for the passive elasticity and central A-band location of muscle myofibrils. The molecular mechanism of titin elasticity is not known, but the I-band region of the molecule appears capable of approximately fourfold reversible extension. Such large extensions are likely to involve unfolding of titin domains. In the present experiments, equilibrium unfolding of titin from rabbit skeletal muscles was studied in vitro by fluorescence and circular dichroism spectroscopy, after addition of guanidinium chloride. The data suggest two unfolding transitions, both of which appear cooperative. The second transition is likely to involve complete unfolding of the immunoglobulin- and fibronectin-like domains from which the molecule is composed. The free energy associated with this transition is comparable with the energy required to extend titin molecules to the maximum amount seen in situ.