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Structure of the inner kinetochore CCAN complex assembled onto a centromeric nucleosome

time:2019-12-27 09:01     number of views:

报告人:闫凯歌  英国MRC分子生物学实验室  博士后

邀请人:马聪教授

时间:2019年12月31日(周二) 16:00-17:00

地点:东十一楼(生命学院)二楼221大会议室

报告摘要:

着丝点是参与细胞分裂的重要的大分子机器,它通过着丝粒将染色体连接到纺锤体微管上。 着丝点复合物在特殊的着丝粒Cenp-A核小体上组装,并且在由纺锤体微管介导的染色体分离过程中发挥承重功能。着丝点复合物由内着丝点和外着丝点两部分组成,他们分别与着丝粒染色质和纺锤体微管相互作用。本次报告主要论述由十四个亚基组成的酿酒酵母内着丝点CCAN-Cenp-A复合物的高分辨冷冻电镜结构,其内部亚复合物的相互依存关系,以及CCANCenp-A核小体之间的相互作用,进一步揭示着丝点复合物在染色体分离过程中发挥的分子功能。


Kinetochores are large protein complexes that attach chromosomes, through their centromeres, to the mitotic spindle. By assembling onto the specialized centromeric Cenp-A nucleosome, kinetochores provide load-bearing structures for microtubule-mediated chromosome segregation in mitosis. The inner and outer kinetochores are responsible for interacting with centromeric chromatin and microtubules, respectively. We have reconstituted the inner kinetochore onto a specialised Cenp-A nucleosome. I will describe the cryo-EM structure of the S. cerevisiae inner kinetochore 14-subunit CCAN complex assembled onto a Cenp-A nucleosome. The structure explains the inter-dependency of CCAN constituent sub-complexes and how the inner kinetochore interacts with the octameric Cenp-A nucleosome. The CCAN–Cenp-A structure provides a framework for understanding how kinetochores link centromeres to microtubules for chromosome segregation.


报告人简介:

2011年毕业于南开大学并取得学士学位。随后进入清华大学生命科学学院,高宁教授和雷建林教授课题组,攻读生物物理学博士学位。在学期间,主要利用冷冻电镜三维重构方法分析大型复合物的高分辨率结构,辅助遗传学、生化分子生物学手段回答大分子机器分子工作机制。2016年博士毕业后,进入英国MRC 分子生物学实验室Prof. David Barford课题组从事博士后研究工作。博士后期间,主要致力于体外重组着丝点相关的大分子蛋白复合物,并探究其结构和功能。目前多个相关研究成果已陆续发表于Nature (2019)Nature Structural & Molecular Biology (20162018) 以及 Nucleic Acids Research (20142015)等高水平生物学期刊上。


代表性论文:

1. Yan, K. †, Yang, J. †, Zhang, Z. †, McLaughlin, S.H., Chang, L., Fasci, D., Ehrenhofer-Murray, A.E., Heck, A.J.R. and Barford, D.. (2019) Structure of the inner kinetochore CCAN complex assembled onto a centromeric nucleosome. Nature, 574, 278-282. († contributed equally to this work).

2. Yan, K. †, Zhang, Z. †, Yang, J., McLaughlin, S.H. and Barford, D.. (2018) Architecture of the CBF3-centromere complex of the budding yeast kinetochore. Nature structural & molecular biology, 25, 1103-1110.

3. Zhang, D. †, Yan, K. †, Liu, G., Song, G., Luo, J., Shi, Y., Cheng, E., Wu, S., Jiang, T., Lou, J., Gao, N. and Qin, Y.. (2016) EF4 disengages the peptidyl-tRNA CCA end and facilitates back-translocation on the 70S ribosome. Nature structural & molecular biology, 23, 125-131.

4. Zhang, D. †, Yan, K. †, Zhang, Y. †, Liu, G., Cao, X., Song, G., Xie, Q., Gao, N. and Qin, Y.. (2015) New insights into the enzymatic role of EF-G in ribosome recycling. Nucleic acids research, 43, 10525-10533.

5. Zhang, X. †, Yan, K. †, Zhang, Y., Li, N., Ma, C., Li, Z., Feng, B., Liu, J., Sun, Y., Xu, Y., Lei, J. and Gao, N.. (2014) Structural insights into the function of a unique tandem GTPase EngA in bacterial ribosome assembly. Nucleic acids research, 42, 13430-13439.