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首页> 外文期刊>Nature >Structure of tubulin at 6.5 A and location of the taxol-binding site.
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Structure of tubulin at 6.5 A and location of the taxol-binding site.

机译：微管蛋白在6.5 A处的结构和紫杉醇结合位点的位置。

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Tubulin, the major component of microtubules, is a heterodimer of two chains, alpha and beta, both of relative molecular mass 50,000 (Mr50K) and with 40-50% identity. The isotypic variety and conformational flexibility of tubulin have so far made it impossible to obtain crystals for X-ray work. Structural knowledge of tubulin has been limited to about 20 A from X-ray diffraction of oriented microtubules, and from electron microscopy of microtubules and zinc-induced crystalline sheets in negative stain. The sheets consist of protofilaments similar to those in microtubules but associated in an antiparallel arrangement, and their two-dimensional character is ideal for high-resolution electron microscopy. Here we present a three-dimensional reconstruction of tubulin to 6.5 A resolution, obtained by electron crystallography of zinc-induced two-dimensional crystals of the protein. The alpha- and beta-subunits appear topologically similar, in agreement with their sequence homology. Several features can be defined in terms of secondary structure. An apparent alpha-helical portion, adjacent to both interdimer and inter-protofilament contacts, is tentatively attributed to a segment near the carboxy terminus of the protein. We can assign the alpha- and beta-subunits on the basis of projection studies of the binding of taxol, which show one taxol site per tubulin heterodimer, in agreement with the known stoichiometry of taxol in microtubules. These studies indicate that taxol affects the interaction between protofilaments; to our knowledge, this is the first time that a ligand-binding site has been visualized in the tubulin molecule.
机译：微管的主要成分微管蛋白是两条链的α和β异源二聚体，两者的相对分子质量均为50,000（Mr50K），且具有40-50％的同一性。迄今为止，微管蛋白的同型多样性和构象柔韧性使得不可能获得用于X射线工作的晶体。根据定向微管的X射线衍射，以及微管和负染色的锌诱导结晶片的电子显微镜，微管蛋白的结构知识仅限于约20A。薄片由与微管中的原丝相似的原丝组成，但以反平行排列相关，它们的二维特性是高分辨率电子显微镜的理想选择。在这里，我们提出了微管蛋白的三维重建至6.5 A的分辨率，这是通过锌的蛋白质二维晶体的电子晶体学获得的。 α-和β-亚基在拓扑上看起来相似，与其序列同源性一致。可以根据二级结构定义几个特征。与二聚体间和原丝间接触相邻的表观α-螺旋部分暂时归因于蛋白质羧基末端附近的区段。我们可以根据紫杉醇结合的投射研究分配α-和β-亚基，与微管中已知的紫杉醇化学计量相符，紫杉醇每个微管蛋白异二聚体显示一个紫杉醇位点。这些研究表明，紫杉酚会影响原丝之间的相互作用。据我们所知，这是第一次在微管蛋白分子中观察到配体结合位点。

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