Structural and functional insights into yeast Tbf1 as an atypical telomeric repeat-binding factor

Zhenfang Wu; Xin Gu; Lin Zha; Qingqiu Yang; Yuanze Zhou; Zhixiong Zeng

doi:10.1016/j.str.2024.04.002

Structural and functional insights into yeast Tbf1 as an atypical telomeric repeat-binding factor

Structure. 2024 Apr 17:S0969-2126(24)00128-X. doi: 10.1016/j.str.2024.04.002. Online ahead of print.

Authors

Zhenfang Wu¹, Xin Gu², Lin Zha³, Qingqiu Yang⁴, Yuanze Zhou⁵, Zhixiong Zeng⁶

Affiliations

¹ Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China. Electronic address: zhenfwu@ucas.ac.cn.
² State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
³ Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China.
⁴ Department of Hematology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China.
⁵ Department of Hematology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China. Electronic address: zhou_yuanze@163.com.
⁶ Hunan Provincial Key Laboratory of the TCM Agricultural Biogenomics, Changsha Medical University, Changsha 410219, China. Electronic address: zengzx@126.com.

PMID: 38677290
DOI: 10.1016/j.str.2024.04.002

Abstract

Telomeric repeat-binding factor 1 (Tbf1) has a similar architecture as the TRF family of telomeric proteins and plays important roles in both telomere homeostasis and ribosome regulation. However, the molecular basis of why Tbf1 has such different functions compared to other TRFs remains unclear. Here, we present the crystal structures of the TRF homology (TRFH) and Myb-L domains from Schizosaccharomyces pombe Tbf1 (spTbf1). TRFH-mediated homodimerization is essential for spTbf1 stability. Importantly, spTbf1_TRFH lacks the conserved docking motif for interactions with telomeric proteins, explaining why spTbf1 does not participate in the assembly of the shelterin complex. Finally, structural and biochemical analyses demonstrate that TRFH and Myb-L domains as well as the loop region of spTbf1 coordinate to recognize S. pombe telomeric double-stranded DNA. Overall, our findings provide structural and functional insights into how fungi Tbf1 acts as an atypical telomeric repeat-binding factor, which helps to understand the evolution of TRFH-containing telomeric proteins.