A TOG:αβ-tubulin complex structure reveals conformation-based mechanisms for a microtubule polymerase.

A TOG:αβ-tubulin complex structure reveals conformation-based mechanisms for a microtubule polymerase.
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DOI:
10.1126/science.1221698
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发表时间:
2012-08-17
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Rice LM
Rice LM
中科院分区:
其他
文献类型:
--
作者:
Ayaz P;Ye X;Huddleston P;Brautigam CA;Rice LM

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Stu 2 p/XMAP 215/Dis 1家族蛋白是进化上保守的调节因子,其使用αβ-微管蛋白相互作用肿瘤过表达基因(TOG)结构域来催化微管快速生长。催化作用要求这些聚合酶区分αβ-微管蛋白的未聚合和聚合形式,但它们这样做的机制仍不清楚。在这里,我们报告了结合到酵母αβ-微管蛋白的Stu 2 p的TOG 1结构域的结构。TOG 1以排除第二TOG结构域的等效结合的方式结合αβ-微管蛋白。此外,TOG 1优先结合不能掺入微管的αβ-微管蛋白的弯曲构象,接触不参与微管组装的α和β-微管蛋白表面。与αβ-微管蛋白的构象选择性相互作用解释了含TOG的聚合酶如何区分αβ-微管蛋白的未聚合和聚合形式,以及它们如何选择性地识别微管的生长末端。
Stu2p/XMAP215/Dis1 family proteins are evolutionarily conserved regulatory factors that use αβ-tubulin–interacting tumor overexpressed gene (TOG) domains to catalyze fast microtubule growth. Catalysis requires that these polymerases discriminate between unpolymerized and polymerized forms of αβ-tubulin, but the mechanism by which they do so has remained unclear. Here, we report the structure of the TOG1 domain from Stu2p bound to yeast αβ-tubulin. TOG1 binds αβ-tubulin in a way that excludes equivalent binding of a second TOG domain. Furthermore, TOG1 preferentially binds a curved conformation of αβ-tubulin that cannot be incorporated into microtubules, contacting α- and β-tubulin surfaces that do not participate in microtubule assembly. Conformation-selective interactions with αβ-tubulin explain how TOG-containing polymerases discriminate between unpolymerized and polymerized forms of αβ-tubulin and how they selectively recognize the growing end of the microtubule.
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