THE MUSCLE THIN FILAMENT AS A CLASSICAL COOPERATIVE ALLOSTERIC REGULATORY SYSTEM/

It is generally accepted that the regulation of muscle contraction inv olves cooperative and allosteric interactions among the protein compon ents, actin, myosin, tropomyosin and troponin. But, as yet, the indivi dual role of each component has not been clearly identified. Here we c ompare the properties of the components of the muscle regulatory syste m with the corresponding components of two systems, hemoglobin and asp artate transcarbamylase, that are well described by the classical Mono d, Wyman and Changeux (MWC) model. The analogy indicates that actin is the catalytic subunit, tropomyosin is the regulatory subunit and trop onin in the absence and presence of Ca2+ is the allosteric inhibitor a nd activator, respectively. The analogy additionally indicates that th e substrate is myosin-Am (or myosin-ADP-Pi) rather than Am. Also, in c ontrast to other MWC systems, the activating ligand for actin-tropomyo sin is a myosin-nucleotide intermediate or product that binds tightly to actin, rather than the substrate which binds weakly. This tightly b ound intermediate switches the system from the off-state to the on-sta te (T tb R-state in MWC nomenclature) in a concerted transition, affec ting n actin subunits, allowing force to be developed. (C) 1998 Academ ic Press Limited.