Volume 27, No 12, Dec 2017
ISSN: 1001-0602
EISSN: 1748-7838 2018
impact factor 17.848*
(Clarivate Analytics, 2019)
Volume 27 Issue 12, December 2017: 1503-1520
ORIGINAL ARTICLES
Structure of the fission yeast S. pombe telomeric Tpz1-Poz1-Rap1 complex
Jing Xue1,2,*, Hongwen Chen1,2,*, Jian Wu3, Miho Takeuchi4, Haruna Inoue4, Yanmei Liu1,2, Hong Sun5, Yong Chen1,2,5, Junko Kanoh4, Ming Lei3,6
1National Center for Protein Science Shanghai, State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese
Academy of Sciences, 333 Haike Road, Shanghai 201210, China;
2Shanghai Science Research Center, Chinese Academy of Sciences, Shanghai, China;
3Shanghai Institute of Precision Medicine, Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200125, China;
4Institute for Protein Research, Osaka University, Suita, Osaka 565-0871, Japan;
5School of Life Science and Technology, ShanghaiTech University, 100 Haike Road, Shanghai 201210, China;
6Key laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
Correspondence: Ming Lei, E-mail: leim@shsmu.edu.cn; Junko Kanoh, E-mail: jkanoh@protein.osaka-u.ac.jp; Yong Chen,(yongchen@sibcb.ac.cn)
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.
10.1038/cr.2017.145
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