STRUCTURAL AND FUNCTIONAL-RESPONSES OF MAMMALIAN THICK FILAMENTS TO ALTERATIONS IN MYOSIN REGULATORY LIGHT-CHAINS

The ordered array of myosin heads, characteristic of relaxed striated muscle thick filaments, is reversibly disordered by phosphorylating my osin regulatory light chains, decreasing temperature and/or ionic stre ngth, increasing pH, and depleting nucleotide, In the case of light ch ain phosphorylation, disorder, most likely due to a change in charge a ffecting the light chain amino-terminus, reflects increased myosin hea d mobility, thus increased accessibility to actin, and results in incr eased calcium sensitivity of tension development. Thus, interactions b etween the unphosphorylated regulatory light chain and the filament ba ckbone may help maintain the overall order of the relaxed filament, To define this relationship, we have examined the structural and functio nal effects of such manipulations as exchanging wild-type smooth and s keletal 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 bio psied fibers from patients with severe familial hypertrophic cardiomyo pathy 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 provid e for evolutionary preservation of this function in vertebrate striate d muscle. (C) 1998 Academic Press.