The On-Off Switch in Regulated Myosins: Different Triggers but Related Mechanisms |
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Authors: | Daniel M. Himmel Suet Mui |
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Affiliation: | Rosenstiel Basic Medical Sciences Research Center, Biology Department, Brandeis University, Waltham, MA 02453-2728, USA |
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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. |
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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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