title: Atomic model of a myosin filament in the relaxed state.
abstract: Contraction of muscle involves the cyclic interaction of myosin heads on the thick filaments with actin subunits in the thin filaments. Muscles relax when this interaction is blocked by molecular switches on either or both filaments. Insight into the relaxed (switched OFF) structure of myosin has come from electron microscopic studies of smooth muscle myosin molecules, which are regulated by phosphorylation. These studies suggest that the OFF state is achieved by an asymmetric, intramolecular interaction between the actin-binding region of one head and the converter region of the other, switching both heads off. Although this is a plausible model for relaxation based on isolated myosin molecules, it does not reveal whether this structure is present in native myosin filaments. Here we analyse the structure of a phosphorylation-regulated striated muscle thick filament using cryo-electron microscopy. Three-dimensional reconstruction and atomic fitting studies suggest that the 'interacting-head' structure is also present in the filament, and that it may underlie the relaxed state of thick filaments in both smooth and myosin-regulated striated muscles over a wide range of species.
authors.affiliation: Department of Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
authors.forename: John L
authors.initials: JL
authors.lastname: Woodhead
authors.forename: Fa-Qing
authors.initials: FQ
authors.lastname: Zhao
authors.forename: Roger
authors.initials: R
authors.lastname: Craig
authors.forename: Edward H
authors.initials: EH
authors.lastname: Egelman
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Alamo
authors.forename: Raúl
authors.initials: R
authors.lastname: Padrón
mesh_terms: D000818:Animals; D020285:Cryoelectron Microscopy; D008958:Models, Molecular; D018482:Muscle, Skeletal / Q000737:chemistry* / Q000648:ultrastructure*; D009130:Muscle, Smooth / Q000737:chemistry / Q000648:ultrastructure; D009218:Myosins / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure*; D010766:Phosphorylation; D020836:Protein Structure, Quaternary; D013112:Spiders
chemical_list: D009218:Myosins