Weisbrich Anke, Honnappa Srinivas, Jaussi Rolf, Okhrimenko Oksana, Frey Daniel, Jelesarov Ilian, Akhmanova Anna, Steinmetz Michel O
Biomolecular Research, Structural Biology, Paul Scherrer Insititut, CH-5232 Villigen PSI, Switzerland.
Nat Struct Mol Biol. 2007 Oct;14(10):959-67. doi: 10.1038/nsmb1291. Epub 2007 Sep 9.
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.
在所有真核生物中，CAP-Gly蛋白控制着重要的细胞过程。然而，CAP-Gly结构域功能背后的分子机制仍知之甚少。在这里，我们以p150（glued）的CAP-Gly结构域与CLIP170的C端锌指结构之间形成的复合物为模型系统，来探索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结构域保守的GKNDG基序负责靶向CLIP170、EB蛋白和微管的C端EEY/F序列基序。CAP-Gly-EEY/F相互作用对于CLIP170募集动力蛋白复合体以及激活CLIP170至关重要。我们的研究结果确定了CAP-Gly结构域功能的分子基础，包括微管蛋白去酪氨酸化-酪氨酸化循环。它们进一步确立了CAP-Gly蛋白与C端EEY/F序列基序之间的相互作用在调节复杂且动态的细胞过程中的基本作用。
