One of the putative actin-binding sites of Dictyostelium myosin II is the -strand-turn--strand structure (Ile 398 -Leu-Ala-Gly-Arg-Asp 403 -Leu-Val 405 ), the "myopathy loop," which is located at the distal end of the upper 50-kDa subdomain and next to the conserved arginine (Arg 397 ), whose mutation in human cardiac myosin results in familial hypertrophic cardiomyopathy. The myopathy loop contains the TEDS residue (Asp 403 ), which is a target of the heavy-chain kinase in myosin I. Moreover, the loop contains a cluster of hydrophobic residues (Ile 398 , Leu 399 , Leu 404 , and Val 405 ), whose side chains are fully exposed to the solvent. In our study, the myopathy loop was deleted from Dictyostelium myosin II to investigate its functional roles. The mutation abolished hydrophobic interactions of actin and myosin in the strong binding state during the ATPase cycle. Association of the mutant myosin and actin was maintained only through ionic interactions under these conditions. Without strong hydrophobic interactions, the mutant myosin still exhibited motor functions, although at low levels. It is likely that the observed defects resulted mainly from a loss of the cluster of hydrophobic residues, since replacement of Asp 403 or Arg 402 with alanine generated a mutant with less severe or no defects compared with those of the deletion mutant.
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