title: The muscle thin filament as a classical cooperative/allosteric regulatory system.
abstract: It is generally accepted that the regulation of muscle contraction involves cooperative and allosteric interactions among the protein components, actin, myosin, tropomyosin and troponin. But, as yet, the individual role of each component has not been clearly identified. Here we compare the properties of the components of the muscle regulatory system with the corresponding components of two systems, hemoglobin and aspartate transcarbamylase, that are well described by the classical Monod, Wyman and Changeux (MWC) model. The analogy indicates that actin is the catalytic subunit, tropomyosin is the regulatory subunit and troponin in the absence and presence of Ca2+ is the allosteric inhibitor and activator, respectively. The analogy additionally indicates that the substrate is myosin-ATP (or myosin-ADP-Pi) rather than ATP. Also, in contrast to other MWC systems, the activating ligand for actin-tropomyosin is a myosin-nucleotide intermediate or product that binds tightly to actin, rather than the substrate which binds weakly. This tightly bound intermediate switches the system from the off-state to the on-state (T to R-state in MWC nomenclature) in a concerted transition, affecting n actin subunits, allowing force to be developed.
authors.affiliation: Muscle Research Group, Boston Biomedical Research Institute, Boston, MA 01224, USA.
authors.forename: S S
authors.initials: SS
authors.lastname: Lehrer
authors.forename: M A
authors.initials: MA
authors.lastname: Geeves
mesh_terms: D000199:Actins / Q000378:metabolism; D000205:Actomyosin / Q000502:physiology; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000494:Allosteric Regulation / Q000502:physiology; D001221:Aspartate Carbamoyltransferase / Q000737:chemistry; D002118:Calcium / Q000378:metabolism; D006454:Hemoglobins / Q000737:chemistry; D007700:Kinetics; D008954:Models, Biological; D009119:Muscle Contraction / Q000502:physiology*; D009124:Muscle Proteins / Q000502:physiology*; D011485:Protein Binding / Q000502:physiology; D014335:Tropomyosin / Q000378:metabolism; D014336:Troponin / Q000378:metabolism
chemical_list: D000199:Actins; D006454:Hemoglobins; D009124:Muscle Proteins; D014335:Tropomyosin; D014336:Troponin; D000255:Adenosine Triphosphate; D000205:Actomyosin; D001221:Aspartate Carbamoyltransferase; D000251:Adenosine Triphosphatases; D002118:Calcium