O'Halloran T J, Ravid S, Spudich J A
Department of Cell Biology, Stanford University School of Medicine, California 94305.
J Cell Biol. 1990 Jan;110(1):63-70. doi: 10.1083/jcb.110.1.63.
The assembly of myosins into filaments is a property common to all conventional myosins. The ability of myosins to form filaments is conferred by the tail of the large asymmetric molecule. We are studying cloned portions of the Dictyostelium myosin gene expressed in Escherichia coli to investigate functional properties of defined segments of the myosin tail. We have focused on five segments derived from the 68-kD carboxyl-terminus of the myosin tail. These have been expressed and purified to homogeneity from E. coli, and thus the boundaries of each segment within the myosin gene and protein sequence are known. We identified an internal 34-kD segment of the tail, N-LMM-34, which is required and sufficient for assembly. This 287-amino acid domain represents the smallest tail segment purified from any myosin that is capable of forming highly ordered paracrystals characteristic of myosin. Because the assembly of Dictyostelium myosin can be regulated by phosphorylation of the heavy chain, we have studied the in vitro phosphorylation of the expressed tail segments. We have determined which segments are phosphorylated to a high level by a Dictyostelium myosin heavy chain kinase purified from developed cells. While LMM-68, the 68-kD carboxyl terminus of Dictyostelium myosin, or LMM-58, which lacks the 10-kD carboxyl terminus of LMM-68, are phosphorylated to the same extent as purified myosin, subdomains of these segments do not serve as efficient substrates for the kinase. Thus LMM-58 is one minimal substrate for efficient phosphorylation by the myosin heavy chain kinase purified from developed cells. Taken together these results identify two functional domains in Dictyostelium myosin: a 34-kD assembly domain bounded by amino acids 1533-1819 within the myosin sequence and a larger 58-kD phosphorylation domain bounded by amino acids 1533-2034 within the myosin sequence.
肌球蛋白组装成丝是所有传统肌球蛋白共有的特性。肌球蛋白形成丝的能力由大型不对称分子的尾部赋予。我们正在研究在大肠杆菌中表达的盘基网柄菌肌球蛋白基因的克隆片段,以研究肌球蛋白尾部特定片段的功能特性。我们聚焦于源自肌球蛋白尾部68-kD羧基末端的五个片段。这些片段已在大肠杆菌中表达并纯化至同质,因此肌球蛋白基因和蛋白质序列中每个片段的边界是已知的。我们鉴定出尾部的一个内部34-kD片段,即N-LMM-34,它是组装所必需且足够的。这个287个氨基酸的结构域代表了从任何能够形成肌球蛋白特有的高度有序副晶体的肌球蛋白中纯化出的最小尾部片段。由于盘基网柄菌肌球蛋白的组装可通过重链的磷酸化来调节,我们研究了表达的尾部片段的体外磷酸化。我们已经确定了哪些片段被从发育细胞中纯化的盘基网柄菌肌球蛋白重链激酶高水平磷酸化。虽然盘基网柄菌肌球蛋白的68-kD羧基末端LMM-68,或缺少LMM-68的10-kD羧基末端的LMM-58,与纯化的肌球蛋白磷酸化程度相同,但这些片段的亚结构域并不是该激酶的有效底物。因此,LMM-58是从发育细胞中纯化的肌球蛋白重链激酶进行有效磷酸化的一个最小底物。综合这些结果,确定了盘基网柄菌肌球蛋白中的两个功能结构域:一个34-kD的组装结构域,在肌球蛋白序列中由氨基酸1533 - 1819界定;一个更大的58-kD的磷酸化结构域,在肌球蛋白序列中由氨基酸1533 - 2034界定。