Structure-function relationship of CAP-Gly domains
Structure-function relationship of CAP-Gly domains
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DOI：
10.1038/nsmb1291
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发表时间：
2007-10-01
影响因子：
16.8
通讯作者：
Steinmetz, Michel O.
中科院分区：
文献类型：
--
作者：
Weisbrich, Anke;Honnappa, Srinivas;Steinmetz, Michel O.
在所有真核生物中，CAP-Gly蛋白控制重要的细胞过程。然而，CAP-Gly结构域功能的分子机制仍然知之甚少。本文以p150的CAP-Gly结构域与CLIP 170的C端锌指形成的复合物为模型系统，探讨CAP-Gly介导的蛋白质相互作用的结构-功能关系。我们证明CAP-Gly结构域的保守GKNDG基序负责靶向CLIP 170、EB蛋白和微管的C-末端EEY/F序列基序。CAP-Gly-EEY/ F相互作用对于由CLIP 170募集dynactin复合物和激活CLIP 170是必需的。我们的研究结果定义了CAP-Gly结构域功能的分子基础，包括微管蛋白脱酪氨酸-酪氨酸周期。他们进一步确立了CAP-Gly蛋白和C-末端EEY/F序列基序在调节复杂和动态细胞过程中相互作用的基本作用。
In all eukaryotes, CAP-Gly proteins control important cellular processes. The molecular mechanisms underlying the functions of CAP-Gly domains, however, are still poorly understood. Here we use the complex formed between the CAP-Gly domain of p150(glued) and the C-terminal zinc knuckle of CLIP170 as a model system to explore the structure-function relationship of CAP-Gly-mediated protein interactions. We demonstrate that the conserved GKNDG motif of CAP-Gly domains is responsible for targeting to the C-terminal EEY/F sequence motifs of CLIP170, EB proteins and microtubules. The CAP-Gly-EEY/ F interaction is essential for the recruitment of the dynactin complex by CLIP170 and for activation of CLIP170. Our findings define the molecular basis of CAP-Gly domain function, including the tubulin detyrosination-tyrosination cycle. They further establish fundamental roles for the interaction between CAP-Gly proteins and C-terminal EEY/F sequence motifs in regulating complex and dynamic cellular processes.