Structural and functional responses of mammalian thick filaments to alterations in myosin regulatory light chains

Rhea J C Levine, Zhaohui Yang, Neal D. Epstein, Lameh Fananapazir, James T. Stull, H. Lee Sweeney

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

The ordered array of myosin heads, characteristic of relaxed striated muscle thick filaments, is reversibly disordered by phosphorylating myosin regulatory light chains, decreasing temperature and/or ionic strength, increasing pH, and depleting nucleotide. In the case of light chain phosphorylation, disorder, most likely due to a change in charge affecting the light chain amino-terminus, reflects increased myosin head mobility, thus increased accessibility to actin, and results in increased calcium sensitivity of tension development. Thus, interactions between the unphosphorylated regulatory light chain and the filament backbone may help maintain the overall order of the relaxed filament. To define this relationship, we have examined the structural and functional effects of such manipulations as exchanging wild-type smooth and skeletal myosin light chains into permeabilized rabbit psoas fibers and removing regulatory light chains (without exchange) from such fibers. We have also compared the structural and functional parameters of biopsied fibers from patients with severe familial hypertrophic cardiomyopathy due to a single amino acid substitution in the regulatory light chains to those exhibited by fibers from normal relatives. Our results support a role for regulatory light chains in reversible ordering of myosin heads and suggest that economy of energy utilization may provide for evolutionary preservation of this function in vertebrate striated muscle.

Original languageEnglish (US)
Pages (from-to)149-161
Number of pages13
JournalJournal of Structural Biology
Volume122
Issue number1-2
DOIs
StatePublished - Jan 1 1998

Keywords

  • Exchanged
  • Expressed
  • Familial hypertrophic cardiomyopathy
  • Mutant myosin regulatory light chains
  • Thick filaments
  • Wild-type

ASJC Scopus subject areas

  • Structural Biology

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