TBCB 的自动抑制调节 EB1 介导的微管动态。
Autoinhibition of TBCB regulates EB1-mediated microtubule dynamics.
机构信息
Departamento de Biología Molecular, Facultad de Medicina, IFIMAV-Universidad de Cantabria, 39011, Santander, Spain.
出版信息
Cell Mol Life Sci. 2013 Jan;70(2):357-71. doi: 10.1007/s00018-012-1114-2. Epub 2012 Sep 1.
Abstract
Tubulin cofactors (TBCs) participate in the folding, dimerization, and dissociation pathways of the tubulin dimer. Among them, TBCB and TBCE are two CAP-Gly domain-containing proteins that together efficiently interact with and dissociate the tubulin dimer. In the study reported here we showed that TBCB localizes at spindle and midzone microtubules during mitosis. Furthermore, the motif DEI/M-COO(-) present in TBCB, which is similar to the EEY/F-COO(-) element characteristic of EB proteins, CLIP-170, and α-tubulin, is required for TBCE-TBCB heterodimer formation and thus for tubulin dimer dissociation. This motif is responsible for TBCB autoinhibition, and our analysis suggests that TBCB is a monomer in solution. Mutants of TBCB lacking this motif are derepressed and induce microtubule depolymerization through an interaction with EB1 associated with microtubule tips. TBCB is also able to bind to the chaperonin complex CCT containing α-tubulin, suggesting that it could escort tubulin to facilitate its folding and dimerization, recycling or degradation.
摘要
微管相关蛋白（TBCs）参与微管二聚体的折叠、二聚和解离途径。其中，TBCB 和 TBCE 是两个含有 CAP-Gly 结构域的蛋白，它们可以有效地相互作用并使微管二聚体解离。在本研究中，我们发现 TBCB 在有丝分裂期间定位于纺锤体和中间区微管。此外，TBCB 中存在与 EB 蛋白、CLIP-170 和α-微管蛋白特征性的 EEY/F-COO(-) 元件相似的 DEI/M-COO(-) 基序，该基序对于 TBCE-TBCB 异二聚体的形成和微管二聚体的解离是必需的。这个基序负责 TBCB 的自身抑制，我们的分析表明 TBCB 在溶液中是单体。缺乏该基序的 TBCB 突变体被解除抑制，并通过与微管尖端相关的 EB1 相互作用诱导微管解聚。TBCB 还能够与含有α-微管蛋白的伴侣蛋白复合物 CCT 结合，表明它可以护送微管，促进其折叠和二聚体形成、回收或降解。
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