Kull F J, Sablin E P, Lau R, Fletterick R J, Vale R D
Department of Biochemistry/Biophysics, University of California, San Francisco, California 94143, USA.
Nature. 1996 Apr 11;380(6574):550-5. doi: 10.1038/380550a0.
Kinesin is the founding member of a superfamily of microtubule based motor proteins that perform force-generating tasks such as organelle transport and chromosome segregation. It has two identical approximately 960-amino-acid chains containing an amino-terminal globular motor domain, a central alpha-helical region that enables dimer formation through a coiled-coil, and a carboxy-terminal tail domain that binds light chains and possibly an organelle receptor. The kinesin motor domain of approximately 340 amino acids, which can produce movement in vitro, is much smaller than that of myosin (approximately 850 amino acids) and dynein (1,000 amino acids), and is the smallest known molecular motor. Here, we report the crystal structure of the human kinesin motor domain with bound ADP determined to 1.8-A resolution by X-ray crystallography. The motor consists primarily of a single alpha/beta arrowhead-shaped domain with dimensions of 70 x 45 x 45 A. Unexpectedly, it has a striking structural similarity to the core of the catalytic domain of the actin-based motor myosin. Although kinesin and myosin have virtually no amino-acid sequence++ identity, and exhibit distinct enzymatic and motile properties, our results suggest that these two classes of mechanochemical enzymes evolved from a common ancestor and share a similar force-generating strategy.
驱动蛋白是基于微管的马达蛋白超家族的创始成员，这类蛋白执行诸如细胞器运输和染色体分离等产生力的任务。它有两条相同的、约含960个氨基酸的链，包含一个氨基末端球状马达结构域、一个通过卷曲螺旋形成二聚体的中央α螺旋区域，以及一个结合轻链和可能的细胞器受体的羧基末端尾部结构域。驱动蛋白约340个氨基酸的马达结构域能在体外产生运动，比肌球蛋白（约850个氨基酸）和动力蛋白（1000个氨基酸）的马达结构域小得多，是已知最小的分子马达。在此，我们报告了通过X射线晶体学确定的、分辨率为1.8埃的、结合有ADP的人驱动蛋白马达结构域的晶体结构。该马达主要由一个尺寸为70×45×45埃的单一α/β箭头状结构域组成。出乎意料的是，它与基于肌动蛋白的马达肌球蛋白催化结构域的核心具有显著的结构相似性。尽管驱动蛋白和肌球蛋白几乎没有氨基酸序列同一性，且表现出不同的酶促和运动特性，但我们的结果表明，这两类机械化学酶起源于共同的祖先，并共享相似的产生力策略。
