Inclán Y F, Nogales E
Howard Hughes Medical Institute, Molecular and Cell Biology Department, University of California at Berkeley, CA 94720-3200, USA.
J Cell Sci. 2001 Jan;114(Pt 2):413-22. doi: 10.1242/jcs.114.2.413.
alphabeta-tubulin heterodimers self-assemble to form microtubules nucleated by gamma-tubulin in the cell. Gamma-tubulin is believed to recruit the alphabeta-tubulin dimers that form the minus ends of microtubules, but the molecular mechanism of this action remains a matter of heated controversy. Still less is known about the function and molecular interactions of delta-tubulin and epsilon-tubulin. delta-tubulin may seed the formation of the C triplet tubules in the basal bodies of Chlamydomonas and epsilon-tubulin is known to localize to the centrosome in a cell cycle-dependent manner. Using the structure of alphabeta tubulin as a model, we have analyzed the sequences of gamma-, delta- and epsilon-tubulin in regions corresponding to different polymerization interfaces in the tubulin alphabeta dimer. The sequence comparisons sometimes show clear conservation, pointing to similar types of contacts being functionally important for the new tubulin considered. Conversely, certain surfaces show marked differences that rule out equivalent interactions for non-microtubular tubulins. This sequence/structure analysis has led us to structural models of how these special tubulins may be involved in protein-protein contacts that affect microtubule self-assembly. delta-tubulin most likely interacts longitudinally with alpha-tubulin at the minus ends of microtubules, while epsilon-tubulin most likely binds to the plus end of beta-tubulin. Conservation of key residues in gamma-tubulin suggests that it is capable of longitudinal self-assembly. The implications for the protofilament and template models of nucleation are considered.
αβ微管蛋白异二聚体在细胞中通过γ-微管蛋白成核自组装形成微管。据信γ-微管蛋白招募形成微管负端的αβ微管蛋白二聚体，但其作用的分子机制仍存在激烈争议。关于δ-微管蛋白和ε-微管蛋白的功能及分子相互作用则知之更少。δ-微管蛋白可能在衣藻基体中引发C三联体微管的形成，已知ε-微管蛋白以细胞周期依赖性方式定位于中心体。以αβ微管蛋白的结构为模型，我们分析了γ-、δ-和ε-微管蛋白在与微管蛋白αβ二聚体中不同聚合界面相对应区域的序列。序列比较有时显示出明显的保守性，表明类似类型的接触对于所考虑的新微管蛋白在功能上很重要。相反，某些表面显示出明显差异，排除了非微管微管蛋白的等效相互作用。这种序列/结构分析使我们得出了这些特殊微管蛋白可能如何参与影响微管自组装的蛋白质-蛋白质接触的结构模型。δ-微管蛋白最有可能在微管负端与α-微管蛋白纵向相互作用，而ε-微管蛋白最有可能与β-微管蛋白的正端结合。γ-微管蛋白中关键残基的保守性表明它能够进行纵向自组装。文中考虑了对原纤维和成核模板模型的影响。
