An unstable head-rod junction may promote folding into the compact off-state conformation of regulated myosins.
The N-terminal region of myosin's rod-like subfragment 2 (S2) joins the two heads of this dimeric molecule and is key to its function. Previously, a crystal structure of this predominantly coiled-coil region was determined for a short fragment (51 residues plus a leucine zipper) of the scallop striated muscle myosin isoform. In that study, the N-terminal 10-14 residues were found to be disordered. We have now determined the structure of the same scallop peptide in three additional crystal environments. In each of two of these structures, improved order has allowed visualization of the entire N-terminus in one chain of the dimeric peptide. We have also compared the melting temperatures of this scallop S2 peptide with those of analogous peptides from three other isoforms. Taken together, these experiments, along with examination of sequences, point to a diminished stability of the N-terminal region of S2 in regulated myosins, compared with those myosins whose regulation is thin filament linked. It seems plain that this isoform-specific instability promotes the off-state conformation of the heads in regulated myosins. We also discuss how myosin isoforms with varied thermal stabilities share the basic capacity to transmit force efficiently in order to produce contraction in their on states.
D000595:Amino Acid Sequence; D000818:Animals; D002942:Circular Dichroism; D003460:Crystallization; D018360:Crystallography, X-Ray; D019281:Dimerization; D008969:Molecular Sequence Data; D054792:Muscle, Striated / Q000737:chemistry; D018995:Myosin Heavy Chains / Q000737:chemistry / Q000378:metabolism; D024462:Myosin Type II / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D049897:Pectinidae / Q000737:chemistry; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D017510:Protein Folding; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid; D014961:X-Ray Diffraction
D010446:Peptide Fragments; D020033:Protein Isoforms; D024462:Myosin Type II; D018995:Myosin Heavy Chains