Department of Molecular Physiology & Biophysics, University of Vermont, Burlington, Vermont 05405.
Department of Biochemistry, University of Iowa College of Medicine, Iowa City, Iowa 52242.
J Biol Chem. 2011 Sep 2;286(35):30384-30392. doi: 10.1074/jbc.M111.262899. Epub 2011 Jul 7.
We employed budding yeast and skeletal muscle actin to examine the contribution of the actin isoform to myosin motor function. While yeast and muscle actin are highly homologous, they exhibit different charge density at their N termini (a proposed myosin-binding interface). Muscle myosin-II actin-activated ATPase activity is significantly higher with muscle versus yeast actin. Whether this reflects inefficiency in the ability of yeast actin to activate myosin is not known. Here we optimized the isolation of two yeast myosins to assess actin function in a homogenous system. Yeast myosin-II (Myo1p) and myosin-V (Myo2p) accommodate the reduced N-terminal charge density of yeast actin, showing greater activity with yeast over muscle actin. Increasing the number of negative charges at the N terminus of yeast actin from two to four (as in muscle) had little effect on yeast myosin activity, while other substitutions of charged residues at the myosin interface of yeast actin reduced activity. Thus, yeast actin functions most effectively with its native myosins, which in part relies on associations mediated by its outer domain. Compared with yeast myosin-II and myosin-V, muscle myosin-II activity was very sensitive to salt. Collectively, our findings suggest differing degrees of reliance on electrostatic interactions during weak actomyosin binding in yeast versus muscle. Our study also highlights the importance of native actin isoforms when considering the function of myosins.
我们使用芽殖酵母和骨骼肌肌动蛋白来研究肌动蛋白同工型对肌球蛋白运动功能的贡献。虽然酵母和肌肉肌动蛋白高度同源,但它们在 N 端的电荷密度不同(被认为是肌球蛋白结合界面)。与酵母肌动蛋白相比,肌肉肌球蛋白 II 肌动蛋白激活的 ATP 酶活性显著更高。这种差异是否反映了酵母肌动蛋白激活肌球蛋白的能力较低尚不清楚。在这里,我们优化了两种酵母肌球蛋白的分离方法,以在同质体系中评估肌动蛋白的功能。酵母肌球蛋白 II(Myo1p)和肌球蛋白 V(Myo2p)适应了酵母肌动蛋白降低的 N 端电荷密度,与肌肉肌动蛋白相比,它们在酵母肌动蛋白中的活性更高。将酵母肌动蛋白 N 端的负电荷数量从两个增加到四个(如肌肉肌动蛋白)对酵母肌球蛋白的活性几乎没有影响,而酵母肌动蛋白肌球蛋白界面上带电荷残基的其他取代则降低了活性。因此,酵母肌动蛋白与其天然肌球蛋白结合的效果最佳,这部分依赖于其外域介导的相互作用。与酵母肌球蛋白 II 和肌球蛋白 V 相比,肌肉肌球蛋白 II 的活性对盐非常敏感。总的来说,我们的研究结果表明,在酵母和肌肉中弱肌动球蛋白结合时,对静电相互作用的依赖程度不同。我们的研究还强调了在考虑肌球蛋白功能时,天然肌动蛋白同工型的重要性。