Gelles J, Berliner E, Young E C, Mahtani H K, Perez-Ramirez B, Anderson K
Department of Biochemistry, Center for Complex Systems, Waltham, Massachusetts 02254, USA.
Biophys J. 1995 Apr;68(4 Suppl):276S-281S; discussion 282S.
The oligomeric structure was determined for four recombinant kinesin derivatives containing N-terminal fragments of the kinesin alpha-subunit. Some of the proteins were dimeric (two-headed) molecules with mechanochemical properties similar to those of intact kinesin. Comparison of the primary and quaternary structures of the derivatives with those of intact kinesin suggests that structures distinct from the long alpha-helical coiled-coil rod domain contribute to subunit self-association. Three of the proteins contain a single engineered site for post-translational biotination in vivo; this facilitates analysis of motility in experiments in which the proteins are specifically bound to streptavidin-conjugated microscopic plastic beads. One of the derivatives is monomeric (one-headed); like the two-headed derivatives, it is functional in the motility assay and is a microtubule-dependent ATPase. Unlike intact kinesin and the two-headed derivatives, the one-headed enzyme fails to track microtubule protofilaments. This confirms a prediction of proposed "hand-over-hand" mechanisms of kinesin movement. The ability of molecules with a one-headed solution structure to generate movement is consistent with a translocation-generating conformational change internal to the kinesin head. A simple set of coupling rules can be used to formulate consistent mechano-chemical mechanisms that explain movement by both one- and two-headed kinesin molecules.
确定了四种含有驱动蛋白α亚基N端片段的重组驱动蛋白衍生物的寡聚结构。其中一些蛋白质是二聚体(双头)分子,其机械化学性质与完整驱动蛋白相似。将这些衍生物的一级结构和四级结构与完整驱动蛋白的结构进行比较表明,不同于长α螺旋卷曲螺旋杆结构域的结构有助于亚基自组装。其中三种蛋白质含有一个用于体内翻译后生物素化的单一工程位点;这便于在蛋白质与链霉亲和素偶联的微观塑料珠特异性结合的实验中分析运动性。其中一种衍生物是单体(单头);与双头衍生物一样,它在运动测定中具有功能,是一种微管依赖性ATP酶。与完整驱动蛋白和双头衍生物不同,单头酶无法追踪微管原纤维。这证实了对所提出的驱动蛋白运动“手换手”机制的预测。具有单头溶液结构的分子产生运动的能力与驱动蛋白头部内部产生易位的构象变化一致。一组简单的耦合规则可用于制定一致的机械化学机制,以解释单头和双头驱动蛋白分子的运动。