title: The on-off switch in regulated myosins: different triggers but related mechanisms.
abstract: In regulated myosin, motor and enzymatic activities are toggled between the on-state and off-state by a switch located on its lever arm domain, here called the regulatory domain (RD). This region consists of a long alpha-helical "heavy chain" stabilized by a "regulatory" light chain (RLC) and an "essential" light chain (ELC). The on-state is activated by phosphorylation of the RLC of vertebrate smooth muscle RD or by direct binding of Ca(2+) to the ELC of molluscan RD. Crystal structures are available only for the molluscan RD. To understand in more detail the pathway between the on-state and the off-state, we have now also determined the crystal structure of a molluscan (scallop) RD in the absence of Ca(2+). Our results indicate that loss of Ca(2+) abolishes most of the interactions between the light chains and may increase the flexibility of the RD heavy chain. We propose that disruption of critical links with the C-lobe of the RLC is the key event initiating the off-state in both smooth muscle myosins and molluscan myosins.
authors.affiliation: Rosenstiel Basic Medical Sciences Research Center, Biology Department, Brandeis University, Waltham, MA 02453-2728, USA. himmel@cabm.rutgers.edu
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Himmel
authors.forename: Suet
authors.initials: S
authors.lastname: Mui
authors.forename: Elizabeth
authors.initials: E
authors.lastname: O'Neall-Hennessey
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Szent-Györgyi
authors.forename: Carolyn
authors.initials: C
authors.lastname: Cohen
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D018360:Crystallography, X-Ray; D066298:In Vitro Techniques; D008958:Models, Molecular; D020409:Molecular Motor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D018994:Myosin Light Chains / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D049897:Pectinidae / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D055672:Static Electricity
chemical_list: D020409:Molecular Motor Proteins; D018994:Myosin Light Chains; D011994:Recombinant Proteins; D002118:Calcium