Crossbridge head detachment rate constants determined from a model that explains the behavior of both weakly- and strongly-binding crossbridges.
Experimentally it is observed that the head regions of weakly-binding myosin crossbridges (crossbridges with ATP or ADP.Pi at the nucleotide binding site) are mobile while attached to actin, while strongly-binding crossbridge heads, such as those with PPi or AMP-PNP at the nucleotide binding site, are immobile (Pate and Cooke, Biophys. J., 1988; Fajer et al., Biophys. J., 1988). I postulate that the fundamental difference between weakly- and strongly-binding crossbridges is not their difference in affinity for actin, but the difference in mobility of the myosin heads attached to actin. Because the heads of weakly-binding crossbridges are mobile while attached to actin, the heads function independently and their behavior can be described by a simple independent-head model. With strongly-binding crossbridges, when one head detaches, it cannot re-attach in a position of lesser strain while the other is attached immobile; both heads must be detached concurrently before the crossbridge can relocate to a position of less strain and relax any tension it supports. This makes the heads appear to act cooperatively. A double-headed crossbridge model is presented which takes into account the difference between weakly- and strongly-binding crossbridges. The model is quite successful at describing the experimental data. In particular, for weakly-binding crossbridges the time constant of the response to stretch is shown to be relatively insensitive to ionic strength and for strongly-binding crossbridges, the model predicts with great accuracy the large ionic strength dependence of the rate constant for force decay. When the experimental results are interpreted according to the model, an important conclusion that emerges is that in all cases (for both weakly- and strongly-binding crossbridges) unstrained crossbridge heads in the muscle fiber detach from actin with approximately the same rate constant as myosin subfragment-1 detaches from actin in solution.
Schoenberg
M
M
Laboratory of Physical Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
D000199:Actins; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000818:Animals; D006801:Humans; D008954:Models, Biological; D009119:Muscle Contraction; D009218:Myosins
D000199:Actins; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D009218:Myosins