Role of the essential light chain in the activation of smooth muscle myosin by regulatory light chain phosphorylation |
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| Institution: | 1. The Institute of Molecular Biophysics, Florida State University, Tallahassee, FL 32306-4380, United States;2. Department of Molecular Biology, TPC6, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, United States;3. Health Science Research Facility 130, 149 Beaumont Avenue, Department of Molecular Physiology & Biophysics, University of Vermont, Burlington, VT 05405, United States;1. Institute of Chemical & Engineering Sciences, Agency for Science, Technology and Research (A1STAR), Singapore 627833, Singapore;2. Experimental Therapeutics Centre, Agency for Science, Technology and Research (A1STAR), Singapore 138669, Singapore;3. Division of Structural Biology and Biochemistry, School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637511, Singapore;1. Institute of Fundamental Sciences, Massey University, Private Bag 11-222, Palmerston North, New Zealand;2. Riddet Institute, Massey University, Private Bag 11-222, Palmerston North, New Zealand;1. Department of Biology, University of Rome Tor Vergata, Via Della Ricerca Scientifica, Rome 00133, Italy;2. CASPUR Inter-universities Consortium for Supercomputing Applications, Via dei Tizii 6b, Rome 00185, Italy |
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| Abstract: | The activity of smooth and non-muscle myosin II is regulated by phosphorylation of the regulatory light chain (RLC) at serine 19. The dephosphorylated state of full-length monomeric myosin is characterized by an asymmetric intramolecular head–head interaction that completely inhibits the ATPase activity, accompanied by a hairpin fold of the tail, which prevents filament assembly. Phosphorylation of serine 19 disrupts these head–head interactions by an unknown mechanism. Computational modeling (Tama et al., 2005. J. Mol. Biol. 345, 837–854) suggested that formation of the inhibited state is characterized by both torsional and bending motions about the myosin heavy chain (HC) at a location between the RLC and the essential light chain (ELC). Therefore, altering relative motions between the ELC and the RLC at this locus might disrupt the inhibited state. Based on this hypothesis we have derived an atomic model for the phosphorylated state of the smooth muscle myosin light chain domain (LCD). This model predicts a set of specific interactions between the N-terminal residues of the RLC with both the myosin HC and the ELC. Site directed mutagenesis was used to show that interactions between the phosphorylated N-terminus of the RLC and helix-A of the ELC are required for phosphorylation to activate smooth muscle myosin. |
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| Keywords: | Modeling Motility ATPase Phosphorylation |
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