State Key Laboratory of Molecular Biology, National Center for Protein Science Shanghai, Shanghai Science Research Center, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences; University of Chinese Academy of Sciences, 333 Haike Road, Shanghai 201210, China.
Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Nucleic Acids Res. 2019 Feb 20;47(3):1573-1584. doi: 10.1093/nar/gky1186.
The dynamic association of chromosomes with the nuclear envelope (NE) is essential for chromosome maintenance. Schizosaccharomyces pombe inner nuclear membrane protein Bqt4 plays a critical role in connecting telomeres to the NE, mainly through a direct interaction with the telomeric protein Rap1. Bqt4 also interacts with Lem2 for pericentric heterochromatin maintenance. How Bqt4 coordinates the interactions with different proteins to exert their functions is unclear. Here, we report the crystal structures of the N-terminal domain of Bqt4 in complexes with Bqt4-binding motifs from Rap1, Lem2, and Sad1. The structural, biochemical and cellular analyses reveal that the N-terminal domain of Bqt4 is a protein-interaction module that recognizes a consensus motif and plays essential roles in telomere-NE association and meiosis progression. Phosphorylation of Bqt4-interacting proteins may act as a switch to regulate these interactions during cell cycles. Our studies provide structural insights into the identification and regulation of Bqt4-mediated interactions.
染色体与核膜（NE）的动态关联对于染色体的维持至关重要。酿酒酵母内核膜蛋白 Bqt4 在将端粒与 NE 连接方面起着关键作用，主要通过与端粒蛋白 Rap1 的直接相互作用。Bqt4 还与 Lem2 相互作用以维持着丝粒异染色质。Bqt4 如何协调与不同蛋白质的相互作用以发挥其功能尚不清楚。在这里，我们报告了 Bqt4 的 N 端结构域与 Rap1、Lem2 和 Sad1 的 Bqt4 结合基序复合物的晶体结构。结构、生化和细胞分析表明，Bqt4 的 N 端结构域是一个蛋白质相互作用模块，识别共有基序，并在端粒-NE 关联和减数分裂进程中发挥重要作用。Bqt4 相互作用蛋白的磷酸化可能作为一种开关，在细胞周期中调节这些相互作用。我们的研究为鉴定和调节 Bqt4 介导的相互作用提供了结构见解。
