The Structure and Dynamics of C. elegans Tubulin Reveals the Mechanistic Basis of Microtubule Growth
The Structure and Dynamics of C. elegans Tubulin Reveals the Mechanistic Basis of Microtubule Growth
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DOI：
10.1016/j.devcel.2018.08.023
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发表时间：
2018-10-22
影响因子：
11.8
通讯作者：
Brouhard, Gary J.
中科院分区：
文献类型：
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作者：
Chaaban, Sami;Jariwala, Shashank;Brouhard, Gary J.
微管的动力学不稳定性是真核生物中保守的基本机制。然而，来自不同物种的微管在其生长速率、晶格结构和对GTP水解的反应方面存在差异。因此，我们不知道是什么限制了微管的生长，什么决定了微管的结构，或者动力学不稳定性的机制是否是普遍的。在这里，我们研究了线虫C的微管。elegans，其在体内具有惊人的快速生长速率和非正则晶格。利用重组方法，我们发现C。秀丽线虫微管联合收割机将固有的快速生长与非常频繁的灾难结合在一起。我们解决了C. elegans微管的4.8埃，并发现在侧接触环的序列分歧，其中之一是有序的C。elegans但在其他物种中未解决。我们提供的直接证据表明，C。elegans微管蛋白在溶液中具有更高的自由能，并提出了一种模型，其中侧向接触环的排序激活微管蛋白的生长。
The dynamic instability of microtubules is a conserved and fundamental mechanism in eukaryotes. Yet microtubules from different species diverge in their growth rates, lattice structures, and responses to GTP hydrolysis. Therefore, we do not know what limits microtubule growth, what determines microtubule structure, or whether the mechanisms of dynamic instability are universal. Here, we studied microtubules from the nematode C. elegans, which have strikingly fast growth rates and non-canonical lattices in vivo. Using a reconstitution approach, we discovered that C. elegans microtubules combine intrinsically fast growth with very frequent catastrophes. We solved the structure of C. elegans microtubules to 4.8 angstrom and discovered sequence divergence in the lateral contact loops, one of which is ordered in C. elegans but unresolved in other species. We provide direct evidence that C. elegans tubulin has a higher free energy in solution and propose a model wherein the ordering of lateral contact loops activates tubulin for growth.