CENP-A/N/L/C着丝粒构效解析

蛋白质之间、以及由蛋白质和其他生物分子，形成复杂、动态的超大分子复合体，对其结构、功能和变化规律的认识，是了解生命本质的主要手段。着丝粒是染色质上一个复杂的非膜性细胞器, 含有20多种蛋白质机器，其可塑性调控是细胞增殖、个体发育与物种繁衍的基础。着丝粒蛋白质机器通过衔接异染色质和纺锤体微管结合，在细胞周期中调控染色体的正确分离。其组装可塑性是细胞生物学、表观遗传学及蛋白质科学的研究热点和难点。CENP-A被认为是着丝粒的表观遗传标记，我的近期工作解析了动粒蛋白CENP-N识别CENP-A核小体的结构基础与分子进化机制。以此为契机，我们拟在“国家自然科学基金委员会2019年度项目指南”的引导下, 阐明动态化学修饰调控相关新型蛋白质机器CENP-A/N/L/C组装的识别与效应机制，并解析CENP-A/N/L/C组装的时空动力学特征, 为阐明着丝粒在细胞命运抉过程中的效应机制提供更为详实的证据。

The understanding of its structure, function and changing laws of dynamic super-molecular complexes formed between proteins and proteins and other biomolecules, is the main means to understand the nature of life. The centromere/kinetochore is a complex, dynamic protein machinery in/on chromatin, and its plasticity is the basis of cell proliferation, individual development and species multiplication. The centromere/kinetochore protein machinery orchestrates accurate segregation of chromosomes during mitosis/meiosis in the cell cycle by attaching heterochromatin to spindle microtubules. Its assembly plasticity is a hot research topic in cell biology, epigenetics and protein sciences and it has been in the ascendant for over 30 years. Centromere protein A (CENP-A) is considered as an epigenetic marker of centromere, and my recent work has solved the structural basis for recognition of the CENP-A nucleosome by the kinetochore protein CENP-N. Under the guidance of the National Natural Science Foundation of China’s 2019 Project Guide, we will use this as an opportunity to elucidate the recognition and effect mechanism of CENP-A/N/L/C assembly, which is regulated by dynamic chemical modifications, and to interpret the spatio-temporal dynamics of CENP-A/N/L/C assembly by the techniques such as SNAP-tag or spectra imaging. We will provide more detailed evidence for elucidating the action mechanism of centromere/kinetochore in cell fate decision.