title: Myosin isoforms and the mechanochemical cross-bridge cycle.
abstract: At the latest count the myosin family includes 35 distinct groups, all of which have the conserved myosin motor domain attached to a neck or lever arm, followed by a highly variable tail or cargo binding region. The motor domain has an ATPase activity that is activated by the presence of actin. One feature of the myosin ATPase cycle is that it involves an association/dissociation with actin for each ATP hydrolysed. The cycle has been described in detail for a large number of myosins from different classes. In each case the cycle is similar, but the balance between the different molecular events in the cycle has been altered to produce a range of very different mechanical activities. Myosin may spend most of the ATPase cycle attached to actin (high duty ratio), as in the processive myosin (e.g. myosin V) or the strain-sensing myosins (e.g. myosin 1c). In contrast, most muscle myosins spend 80% of their ATPase cycle detached from actin. Within the myosin IIs found in human muscle, there are 11 different sarcomeric myosin isoforms, two smooth muscle isoforms as well as three non-muscle isoforms. We have been exploring how the different myosin isoforms have adapted the cross-bridge cycle to generate different types of mechanical activity and how this goes wrong in inherited myopathies. The ideas are outlined here.
authors.affiliation: School of Biosciences, University of Kent, Canterbury CT2 7NJ, UK.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Walklate
authors.affiliation: School of Biosciences, University of Kent, Canterbury CT2 7NJ, UK.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Ujfalusi
authors.affiliation: School of Biosciences, University of Kent, Canterbury CT2 7NJ, UK m.a.geeves@kent.ac.uk.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Geeves
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D001696:Biomechanical Phenomena; D006801:Humans; D008954:Models, Biological; D009218:Myosins / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D012518:Sarcomeres / Q000378:metabolism*
chemical_list: D020033:Protein Isoforms; D000244:Adenosine Diphosphate; D009218:Myosins
keywords: Cardiac; Contraction; Human; Muscle; Skeletal