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施一公组Science发文:解析人源剪切体关键机制

2018-01-08 10:30


本文转载自“BioArt”,原标题为:施一公组解析人源剪切体第一步催化激活状态C complex结构。

内含子的去除主要是通过两步转酯反应来实现的,这两步化学反应是由剪接体催化完成的。对于每一个内含子来说,为了调控反应的各个基团在适当时机呈现合适的构象从而发挥其活性,剪接体各组分按照高度精确的顺序结合和解离,组装成一系列具有不同构象的分子机器,统称为剪接体。根据它们在RNA剪接过程中的生化性质,这些剪接体又被区分为E、A、B、Bact、B*、C、C*、P、ILS等若干状态。

与此前报道的酿酒酵母中的C复合体状态结构相比,人源C复合体还包含另外11中蛋白质。第一步反应中的剪接因子CCDC49和CCDC94(酵母中对应为Cwc25和Yju2)与DEAH家族ATP酶/解旋酶Prp16有很紧密的相互作用,并且桥接了Prp16与活性位点的RNA元件中的间隙(下图)。


上述工作连同此前施一公组报道的人源剪接体C*状态的结构,对于深入认识复杂的人源剪接体的工作机理具有重要的意义。

附施一公实验室有关剪接体的论文列表:

1、Yan, C., Hang, J., Wan, R., Huang, M., Wong, C. C., & Shi, Y. (2015). Structure of a yeast spliceosome at 3.6-angstrom resolution. Science, 349(6253), 1182-1191.

2、Hang, J., Wan, R., Yan, C., & Shi, Y. (2015). Structural basis of pre-mRNA splicing. Science, 349(6253), 1191-1198.

3、Wan, R., Yan, C., Bai, R., Wang, L., Huang, M., Wong, C. C., & Shi, Y. (2016). The 3.8 Å structure of the U4/U6. U5 tri-snRNP: Insights into spliceosome assembly and catalysis. Science, 351(6272), 466-475.

4、Yan, C., Wan, R., Bai, R., Huang, G., & Shi, Y. (2016). Structure of a yeast activated spliceosome at 3.5 Å resolution.Science, 353(6302), 904-911.

5、Yan, C., Wan, R., Bai, R., Huang, G., & Shi, Y. (2016). Structure of a yeast step II catalytically activated spliceosome.Science, aak9979.

6、Wan, R., Yan, C., Bai, R., Huang, G., & Shi, Y. (2016). Structure of a yeast catalytic step I spliceosome at 3.4 Å resolution.Science, 353(6302), 895-904.

7、Zhang, X., Yan, C., Hang, J.,Finci, L., Lei, J., & Shi, Y. (2017).An Atomic Structure of the Human Spliceosome.Cell,169, 1–12

8、Wan, R., Yan, C., Bai, R.,Lei, J., & Shi, Y. (2017).Structure of an Intron Lariat Spliceosome from Saccharomyces cerevisiae.Cell,171, 1–13

Bai, R., Yan, C., Wan, R., Lei, J., & Shi, Y. (2017). Structure of the Post-catalytic Spliceosome from Saccharomyces cerevisiae. Cell, 171(7), 1589-1598.

综述:

Shi, Y. (2017). The Spliceosome: A Protein-Directed Metalloribozyme. Journal of Molecular Biology, 429(17), 2640-2653.

Shi, Y. (2017). Mechanistic insights into precursor messenger RNA splicing by the spliceosome. Nature Reviews Molecular Cell Biology, 18(11), 655.

来源:BioArt 点击量:

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