An EB1-Binding Motif Acts as a Microtubule Tip Localization Signal
An EB1-Binding Motif Acts as a Microtubule Tip Localization Signal
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DOI：
10.1016/j.cell.2009.04.065
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发表时间：
2009-07-23
期刊：
影响因子：
64.5
通讯作者：
Steinmetz, Michel O.
中科院分区：
文献类型：
--
作者：
Honnappa, Srinivas;Gouveia, Susana Montenegro;Steinmetz, Michel O.
微管是细胞生存所必需的丝状聚合物。微管加末端跟踪蛋白（+TIPs）与生长的微管加末端相关，并控制微管动力学以及在细胞分裂、迁移和形态发生期间与不同细胞结构的相互作用。EB 1及其同源物是高度保守的蛋白质，在+TIPs靶向微管末端中发挥重要作用，但潜在的分子机制仍然难以捉摸。通过使用活细胞实验和体外重建试验，我们证明了一个短的多肽基序，Ser-x-Ile-Pro（SxIP），是由许多+TIPs，包括肿瘤抑制APC，跨膜蛋白STIM 1，和驱动蛋白MCAK，用于本地化的微管提示在EB 1依赖的方式。结构和生化数据揭示了EB 1-SxIP相互作用的分子基础，并解释了其通过磷酸化的负调控。我们的研究结果建立了一个一般的“微管尖端定位信号”（MtLS），并描绘了一个统一的机制，这种亚细胞蛋白质靶向过程。
Microtubules are filamentous polymers essential for cell viability. Microtubule plus-end tracking proteins (+TIPs) associate with growing microtubule plus ends and control microtubule dynamics and interactions with different cellular structures during cell division, migration, and morphogenesis. EB1 and its homologs are highly conserved proteins that play an important role in the targeting of +TIPs to microtubule ends, but the underlying molecular mechanism remains elusive. By using live cell experiments and in vitro reconstitution assays, we demonstrate that a short polypeptide motif, Ser-x-Ile-Pro (SxIP), is used by numerous +TIPs, including the tumor suppressor APC, the transmembrane protein STIM1, and the kinesin MCAK, for localization to microtubule tips in an EB1-dependent manner. Structural and biochemical data reveal the molecular basis of the EB1-SxIP interaction and explain its negative regulation by phosphorylation. Our findings establish a general "microtubule tip localization signal'' (MtLS) and delineate a unifying mechanism for this subcellular protein targeting process.