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The On-Off Switch in Regulated Myosins: Different Triggers but Related Mechanisms
Authors:Daniel M Himmel  Suet Mui
Institution:Rosenstiel Basic Medical Sciences Research Center, Biology Department, Brandeis University, Waltham, MA 02453-2728, USA
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 α-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 Ca2+ 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 Ca2+. Our results indicate that loss of Ca2+ 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.
Keywords:RD  regulatory domain  RLC  regulatory light chain  HC  heavy chain  ELC  essential light chain  MLCK  myosin light-chain kinase  HMM  heavy meromyosin  cryo-EM  cryo-electron microscopy  EGTA  ethylene glycol bis(b-aminoethyl ether) N  N&prime  -tetraacetic acid  PEG  polyethylene glycol  PDB  Protein Data Bank
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