Vol. 291, Issue 3, 1121-1126, December 1999

Powerful Activation of Skeletal Muscle Actomyosin ATPase by Goniodomin A Is Highly Sensitive to Troponin/Tropomyosin Complex¹

Kimihiro Matsunaga, Keigo Nakatani, Masahiro Murakami, Katsumi Yamaguchi and Yasushi Ohizumi

Department of Pharmaceutical Molecular Biology, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba, Aramaki, Sendai, Japan (K.M., K.N., Y.O.); Laboratory of Marine Biochemistry, Graduate School of Agricultural Life Sciences, The University of Tokyo, Yayoi, Tokyo, Japan (M.M.); and Faculty of Engineering, Tokyo University of Agriculture and Technology, Koganei, Tokyo, Japan (K.Y.)

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 10⁸ to 10⁷ M. When the concentration was increased above 10⁷ 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 10⁸ M increased the negative ellipticity at 220 nm, suggesting an increase in the -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.