Structure of the fission yeast S. pombe telomeric Tpz1-Poz1-Rap1 complex.
Structure of the fission yeast S. pombe telomeric Tpz1-Poz1-Rap1 complex.
复制标题
裂殖酵母粟酒裂殖酵母端粒 Tpz1-Poz1-Rap1 复合物的结构。
DOI：
10.1038/cr.2017.145
复制
发表时间：
2017
期刊：
影响因子：
44.1
通讯作者：
Lei Ming
中科院分区：
文献类型：
--
作者：
Xue Jing;Chen Hongwen;Wu Jian;Takeuchi Miho;Inoue Haruna;Liu Yanmei;Sun Hong;Chen Yong;Kanoh Junko;Lei Ming
端粒掩蔽蛋白复合体覆盖染色体末端，在端粒的维持和保护中起着重要作用。在裂殖酵母裂殖酵母中，shelterin由端粒单链和双链DNA结合蛋白亚复合物Pot 1-Tpz 1和Taz 1-Rap 1组成，它们通过相互作用蛋白Poz 1桥接。然而，Poz 1的结构以及Poz 1如何在shelterin复合体中作为相互作用中心发挥作用仍不清楚。在这里，我们报告的晶体结构的Poz 1在复杂的Poz 1结合图案的TPZ 1和Rap 1。晶体结构表明，Poz 1采用两种不同的结合表面与Tpz 1和Rap 1相互作用。出乎意料的是，该结构还揭示了Poz 1采用二聚体构象。突变分析表明，在shelterin核心复合物中Tpz 1，Poz 1和Rap 1之间的适当相互作用是端粒长度稳态和端粒异染色质结构维持所必需的。Poz 1和其他shelterin蛋白在裂殖酵母和人类的TRFH结构域之间的结构相似性表明了shelterin蛋白进化的模型。
Telomeric shelterin complex caps chromosome ends and plays a crucial role in telomere maintenance and protection. In the fission yeast Schizosaccharomyces pombe, shelterin is composed of telomeric single-and double-stranded DNA-binding protein subcomplexes Pot1-Tpz1 and Taz1-Rap1, which are bridged by their interacting protein Poz1. However, the structure of Poz1 and how Poz1 functions as an interaction hub in the shelterin complex remain unclear. Here we report the crystal structure of Poz1 in complex with Poz1-binding motifs of Tpz1 and Rap1. The crystal structure shows that Poz1 employs two different binding surfaces to interact with Tpz1 and Rap1. Unexpectedly, the structure also reveals that Poz1 adopts a dimeric conformation. Mutational analyses suggest that proper interactions between Tpz1, Poz1, and Rap1 in the shelterin core complex are required for telomere length homeostasis and heterochromatin structure maintenance at telomeres. Structural resemblance between Poz1 and the TRFH domains of other shelterin proteins in fission yeast and humans suggests a model for the evolution of shelterin proteins.