师资队伍

  • 师资队伍

屈前辉

发布者:张弦发布时间:2021-07-25浏览次数:510

屈前辉 (1983-)

青年研究员

地址:上海市东安路130号明道楼507室

邮箱: qqh@fudan.edu.cn

个人简介:

       中科院生物物理所博士,先后在美国德州大学西南医学中心、密歇根大学从事博士后研究,在斯坦福大学担任研究科学家。主要研究领域:表观遗传重要调控大分子复合物和GPCR信号传递的结构生物学。代表性成果:首次解析组蛋白H3K4甲基化酶COMPASS/MLL的高分辨三维结构,探究了三甲基化活性被Cps30/WDR5调控的分子基础(Cell,2018);报道迄今为止唯一的G11-GPCR复合物结构,阐述不同G蛋白亚型介导相同或相似GPCR受体的差异(Science,2019);解析了神经降压素受体NSTR1与Arrestin调控蛋白的复合物结构,阐释了GPCR受体偏向性激活G蛋白或者Arrestin蛋白的机制(Nature, 2020)。

研究方向

       主要研究细胞分裂和基因转录翻译过程中发挥重要作用的分子机器,以及与人类的正常生理功能和疾病发生发展息息相关的G蛋白偶联受体(GPCR)信号传递机制。运用结构生物学中常用的技术方法(冷冻电镜和X射线晶体),获取大分子的高清三维结构信息,并结合细胞生物学、生物化学以及计算机辅助模拟技术手段,探索信号识别传递与基因转录翻译的协调机理,为设计可靠高效的靶向性药物提供基础。

How do cells perceive and respond to extracellular stimuli? In humans, the biggest group of cellular membrane proteins (G-protein coupled receptors) are involved in recognition of numerous signals with diverse identities and initiate distinct signaling cascades. Different epigenetic molecular machineries within nucleus react to these conveyed signals and regulate gene transcription correspondingly. Such cooperation plays essential roles in normal physiology and human diseases. A combination of structural biology (cryo-EM/X-ray crystallography), biochemistry and molecular biology, and computer assisted molecular dynamics simulations have led to our recent progresses, including:1, molecular mechanism of histone H3k4 tri-methylation mediated by COMPASS/MLL complex (Cell, 2018); 2, the unique features of G11 heterotrimer selected by muscarinic acetylcholine receptor 1 (M1R) compared to the close family member Gi-preferred M2R (Science, 2019); 3, structural basis of GPCR downstream ubiquitous effector β-arrestin 1 recognized by neurotensin receptor (Nature, 2020). In future, our interests are to decipher mechanisms underlying the cross-talk between membrane receptors and epigenetic regulators.

代表论文

1、Weijiao Huang#, Matthieu Masureel#, Qianhui Qu#, John Janetzko#, Asuka Inoue, Khanh Nguyen, Hideaki Kato, Jeffrey Glenn, Michael Robertson, Georgios Skiniotis*, Brian K. Kobilka* (2020) Structure of the Neurotensin Receptor 1 in complex with β-arrestin 1. Nature 579, 303–308

2、Shoji Maeda#, Qianhui Qu#, Michael J. Robertson, Georgios Skiniotis*, Brian K. Kobilka* (2019) Structures of the M1 and M2 muscarinic acetylcholine receptor/G-protein complexes. Science Vol. 364, Issue 6440, pp. 552-557

3、Qianhui Qu#, Yohhei Takahashi#, Yidai Yang, Hongli Hu, Yan Zhang, Joseph S Brunzelle, Jean-François Couture, Ali Shilatifard*, Georgios Skiniotis* (2018) Structure and conformational dynamics of COMPASS histone H3K4 methyltransferase. Cell 174(5):1117-1126

4、Qianhui Qu#, Lu Yang#, Qian Zhang, Xiaofeng Zhu, Hong Liu (2019) SET de-protects centromeric cohesion through inhibiting interaction of Sgo1 and cohesin. Journal of Cell Biology DOI: 10.1083/jcb.201810096

5、Antoine Koehl#, Hongli Hu#, Shoji Maeda#, Yan Zhang, Qianhui Qu, Joseph M. Paggi, Naomi Latorraca, Daniel Hilger, Roger Dawson, Hugues Matile, Sebastien Granier, William I. Weis, Ron O. Dror, Aashish Manglik, Georgios Skiniotis*, Brian K. Kobilka* (2018) Structure of the µ Opioid Receptor-Gi Protein Complex. Nature 558, 547-552.

6、Yan Zhang#, Bingfa Sun#, Dan Feng, Hongli Hu, Matthew Chu, Qianhui Qu, Jeffrey T. Tarrasch, Shane Li, Tong Sun Kobilka, Brian K. Kobilka*, Georgios Skiniotis* (2017) Cryo-EM structure of the activated GLP-1 receptor in complex with a G protein. Nature 546, 248-253

7、Hong Liu, Qianhui Qu, Ross Warrington, Allyson Rice, Ningyan Cheng, and Hongtao Yu (2015) Mitosis Transcription Installs Sgo1 at Centromeres to Coordinate Chromosome Segregation. Molecular Cell. 59(3):426-36.

8、Kodai Hara#, Ge Zheng#, Qianhui Qu, Hong Liu, Zhuqing Ouyang, Zhe Chen, Diana R Tomchick & Hongtao Yu (2014) Structure of cohesin subcomplex pinpoints direct shugoshin-Wapl antagonism in centromeric cohesion. Nature Structural & Molecular Biology. 21, 864-870