Sablin E P, Kull F J, Cooke R, Vale R D, Fletterick R J
Department of Biochemistry/Biophysics, University of California, San Francisco, California 94143, USA.
Nature. 1996 Apr 11;380(6574):555-9. doi: 10.1038/380555a0.
Microtubule-based ATPases of the kinesin superfamily provide the motile force for many animated features of living cells. Kinesin motors differ in their direction of movement along microtubules. Kinesin and ncd, a kinesin-related motor involved in formation and maintenance of mitotic and meiotic spindles, move in opposite directions along microtubules, even though their motor domains are 40% identical in amino-acid sequence. Here we report the crystal structure of the MgADP complex of the Drosophila ncd motor domain determined to 2.5A by X-ray crystallography, and compare it to the kinesin structure. The ncd and kinesin motor domains are remarkably similar in structure, and the locations of conserved surface amino acids suggest these motors share a common microtubule-binding site. Moreover, structural and functional comparisons of ncd, kinesin, myosin and G proteins indicate that these NTPases may have a similar strategy of changing conformation between NTP and NDP states. We propose a general model for converting a common gamma-phosphate-sensing mechanism into opposite polarities of movement for kinesin and ncd.
驱动蛋白超家族中基于微管的ATP酶为活细胞的许多动态特征提供动力。驱动蛋白马达沿着微管的运动方向不同。驱动蛋白和ncd（一种与驱动蛋白相关的马达蛋白，参与有丝分裂和减数分裂纺锤体的形成与维持）沿着微管向相反方向移动，尽管它们的马达结构域在氨基酸序列上有40%是相同的。在此，我们报告了通过X射线晶体学确定的果蝇ncd马达结构域的MgADP复合物的晶体结构，分辨率为2.5埃，并将其与驱动蛋白结构进行比较。ncd和驱动蛋白的马达结构域在结构上非常相似，保守表面氨基酸的位置表明这些马达共享一个共同的微管结合位点。此外，对ncd、驱动蛋白、肌球蛋白和G蛋白的结构与功能比较表明，这些NTP酶在NTP和NDP状态之间改变构象可能有相似的策略。我们提出了一个通用模型，用于将共同的γ-磷酸传感机制转化为驱动蛋白和ncd相反的运动极性。
