RT Journal Article
SR Electronic
T1 Powerful Activation of Skeletal Muscle Actomyosin ATPase by Goniodomin A Is Highly Sensitive to Troponin/Tropomyosin Complex
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 1121
OP 1126
VO 291
IS 3
A1 Matsunaga, Kimihiro
A1 Nakatani, Keigo
A1 Murakami, Masahiro
A1 Yamaguchi, Katsumi
A1 Ohizumi, Yasushi
YR 1999
UL http://jpet.aspetjournals.org/content/291/3/1121.abstract
AB Goniodomin A has been shown to cause the conformational change of actin to modify actomyosin ATPase activity. Goniodomin A induced a potent stimulation of the actomyosin ATPase activities of the actin-myosin reconstituted system and natural actomyosin in the range of 10−8 to 10−7 M. When the concentration was increased above 10−7 M, actomyosin ATPase activity was decreased. Interestingly, the troponin/tropomyosin complex caused a concentration-dependent inhibition of the goniodomin A-induced stimulation of actomyosin ATPase activity. In the presence of a high concentration of the troponin/tropomyosin complex, goniodomin A decreased actomyosin ATPase activity in a concentration-dependent manner. The enhancement of the ATPase activity of troponin/tropomyosin-free natural actomyosin by goniodomin A was larger than that obtained with natural actomyosin. Goniodomin A at lower concentrations enhanced the superprecipitation of natural actomyosin but decreased it at higher concentrations. The ATPase activity of skeletal muscle myofibrils and the contractile response of skinned fibers to Ca2+ were never activated and were decreased by this compound, suggesting an inhibition by the troponin/tropomyosin complex. In the far ultraviolet circular dichroism, goniodomin A above 10−8 M increased the negative ellipticity at 220 nm, suggesting an increase in the α-helical content of actin. These results suggest that goniodomin A increases and decreases actomyosin ATPase activity, probably through the stimulatory and inhibitory sites on actin, respectively. It is also suggested that the troponin/tropomyosin complex binds to actin to inhibit the goniodomin A-induced enhancement of actomyosin ATPase activity, probably by affecting the stimulatory site on the molecule. The American Society for Pharmacology and Experimental Therapeutics