THE IN-VITRO MOTILITY ACTIVITY OF BETA-CARDIAC MYOSIN DEPENDS ON THE NATURE OF THE BETA-MYOSIN HEAVY-CHAIN GENE MUTATION IN HYPERTROPHIC CARDIOMYOPATHY

Several mutations in the beta-myosin heavy chain gene cause hypertroph ic cardiomyopathy. This study investigates (1) the in vitro velocities of translocation of fluorescently-labelled actin by beta-myosin purif ied from soleus muscle of 30 hypertrophic cardiomyopathy patients with seven distinct beta-myosin heavy chain gene mutations: Thr124Ile, Tyr 162Cys, Gly256Glu, Arg403Gln, Val606Met, Arg870His, and Leu908Val muta tions; and (2) motility activity of beta-myosin purified from cardiac and soleus muscle biopsies in the same patients. The velocity of trans location of actin by beta-myosin purified from soleus or cardiac muscl e of 22 normal controls was 0.48 +/- 0.09 mu m s(-1). By comparison, t he motility activity was reduced in all 30 patients with beta-myosin h eavy chain gene mutations (range, 0.112 +/- 0.041 to 0.292 +/- 0.066 m u m s(-1)). Notably, the Tyr162Cys and Arg403Gln mutations demonstrate d significantly lower actin sliding velocities: 0.123 +/- 0.044, and 0 .112 +/- 0.041 mu m s(-1), respectively beta-myosin purified from sole us muscle from four patients with the Arg(403)Gln mutation had a simil ar actomyosin motility activity compared to beta-myosin purified from their cardiac biopsies (0.127 +/- 0.045 mu m s(-1) versus 0.119 +/- 0. 068 mu m s(-1), respectively). Since these seven mutations lie in seve ral distinct functional domains, it is likely that the mechanisms of t heir inhibitions of motility are different.