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施一公

 

施一公 

 

电子邮件shi-lab(at)mail(dot)tsinghua(dot)edu(dot)cn
电话:+86-10-62797560(实验室)
实验室主页
http://life.tsinghua.edu.cn/lab/ygshi/home.htm

 

主要科研领域与方向:
主要运用结构生物学和生物化学的手段研究肿瘤发生和细胞调亡的分子机制,集中于肿瘤抑制因子和细胞凋亡调节蛋白的结构和功能研究
与重大疾病相关膜蛋白的结构与功能的研究
细胞内生物大分子机器的结构与功能研究

 

代表性论文:

细胞凋亡领域:

  1. Shiqian Qi, Yuxun Pang, Qi Hu, Qun Liu, Hua Li, Yulian Zhou, Tianxi He, Qionglin Liang, Yexing Liu, Xiaoqiu Yuan, Guoan Luo, Huilin Li, Jiawei Wang, Nieng Yan, and Yigong Shi (2010). Crystal structure of the Caenorhabditis elegans apoptosome reveals an octameric assembly of CED-4. Cell 141, 446-457.
  2. Jong W. Yu, Philip D. Jeffrey, and Yigong Shi (2009). Mechanism of procaspase-8 activation by c-FLIPL. Proc Natl Acad Sci USA 106, 8169-8174. Epub 2009 May 4.
  3. Nieng Yan, Jijie Chai, Eui Seung Lee, Lichuan Gu, Qun Liu, Jiaqing He, Jia-Wei Wu, David Kokel, Huilin Li, Quan Hao, Ding Xue, and Yigong Shi (2005). Structure of the CED-4/CED-9 complex provides insights into programmed cell death in Caenorhabditis elegans. Nature 437, 831–837.
  4. Stefan J. Riedl, Wenyu Li, Yang Chao, Robert Schwarzenbacher, and Yigong Shi (2005). Structure of the apoptotic protease activating factor 1 (Apaf-1) bound to ADP. Nature 434, 926–933.
  5. Nieng Yan, Lichuan Gu, David Kokel, Jijie Chai, Wenyu Li, Aidong Han, Lin Chen, Ding Xue, and Yigong Shi (2004). Structural, Biochemical and Functional Analyses of CED-9 Recognition by the Pro-apoptotic Proteins EGL-1 and CED-4. Mol. Cell 15, 999–1006.
  6. Stefan J. Riedl and Yigong Shi (2004). Molecular mechanisms of caspase regulation during apoptosis. Nature Review – Mol. Cell. Biol. 5, 897–907.
  7. Nieng Yan, Jia-Wei Wu, Jun R. Huh, Jijie Chai, Wenyu Li, Bruce A. Hay, and Yigong Shi (2004). Molecular mechanisms of DrICE inhibition by DIAP1 and removal of inhibition by Reaper, Hid, and Grim. Nature-Structural & Molecular Biology 11 (5), 420–428.
  8. Yigong Shi (2004). Caspase Activation: Revisiting the Induced Proximity model. Cell 117, 855–858.
  9. Jijie Chai, Nieng Yan, Jun R. Huh, Jia-Wei Wu, Wenyu Li, Bruce A. Hay, and Yigong Shi (2003). Molecular mechanism of Reaper/Grim/Hid-mediated suppression of DIAP1-dependent Dronc ubiquitination. Nature-Structural Biology 10, 892-898.
  10. Eric N. Shiozaki, Jijie Chai, Daniel J. Rigotti, Stefan J. Riedl, Pingwei Li, Srinivasa M. Srinivasula, Emad S. Alnemri, Robert Fairman, and Yigong Shi (2003). Mechanism of XIAP-mediated Inhibition of Caspase-9. Mol. Cell 11, 519-527.
  11. Yigong Shi (2002). Mechanisms of Caspase Activation and Inhibition During Apoptosis (commissioned review article). Mol Cell 9, 459-470.
  12. Jijie Chai Qi Wu, Eric Shiozaki, Srinivasa M. Srinivasula, Emad S. Alnemri, and Yigong Shi (2001). Crystal Structure of a Caspase Zymogen: Mechanisms of Activation and Substrate Binding. Cell107, 399-407.
  13. Jia-Wei Wu, Amy Cocina, Jijie Chai, Bruce Hay, and Yigong Shi (2001). Structural Analysis of a Functional DIAP1 Fragment Bound to Grim and Hid Peptides. Mol. Cell 8, 95-104.
  14. Jijie Chai, Eric Shiozaki, Srinivasa M. Srinivasula, Qi Wu, Pinaki Datta, Emad S. Alnemri, and Yigong Shi (2001). Structural Basis of Caspase-7 Inhibition by XIAP. Cell 104, 769-780.
  15. Stephen W. Fesik and Yigong Shi (2001). Controlling the Caspases. Science 294, 1477-1478.
  16. Geng Wu, Jijie Chai, Tomeka Suber, Jia-Wei Wu, Chunying Du, Xiaodong Wang, and Yigong Shi (2000). Structural Basis of IAP Recognition by Smac/DIABLO. Nature408, 1008-1012.
  17. Jijie Chai, Chunying Du, Jia-Wei Wu, Saw Kyin, Xiaodong Wang, and Yigong Shi (2000). Structural and Biochemical Basis of Apoptotic Activation by Smac/DIABLO. Nature 406, 855-862.
  18. Hongxu Qin, Srinivasa M. Srinivasula, Geng Wu, Emad S. Alnemri, Yigong Shi (1999). Structural Basis of Procaspase-9 Recruitment by the Apoptotic Protease Activating Factor 1. Nature 399, 549-557.
 
膜蛋白结构与功能领域:
  1. Peng Zhang, Jiawei Wang, and Yigong Shi (2010). Structure and mechanism of the S component of a bacterial ECF transporter. Nature 468, 717-720. Epub 2010 Oct 24.
  2. Xiang Gao, Lijun Zhou, Xuyao Jiao, Feiran Lu, Chuangye Yan, Xin Zeng, Jiawei Wang, and Yigong Shi (2010). Mechanism of substrate recognition and transport by an amino acid antiporter. Nature 463, 828-832. Epub 2010 Jan 20.
  3. Yi Wang, Yongjian Huang, Jiawei Wang, Chao Cheng, Weijiao Huang, Peilong Lu, Ya-Nan Xu, Pengye Wang, Nieng Yan, and Yigong Shi (2009). Structure of the formate transporter FocA reveals a pentameric aquaporin-like channel.  Nature 462, 467-472.
  4. Xiang Gao, Feiran Lu, Lijun Zhou, Shangyu Dang, Linfeng Sun, Xiaochun Li, Jiawei Wang, and Yigong Shi (2009). Structure and Mechanism of an Amino Acid Antiporter. Science 324, 1565-1568. Epub 2009 May 28.
  5. Xiaochun Li, Boyuan Wang, Lihui Feng, Hui Kang, Yang Qi, Jiawei Wang, and Yigong Shi (2009). Cleavage of RseA by RseP requires a carboxyl-terminal hydrophobic amino acid following DegS cleavage. Proc. Natl. Acad. Sci. USA  106, 14837-42 [Epub 2009 August 18].
  6. Liang Feng, Hanchi Yan, Zhuoru Wu, Nieng Yan, Zhe Wang, Philip D. Jeffrey, and Yigong Shi (2007). Structure of a Site-2 Protease Family Intramembrane Metalloprotease.   Science 318, 1608-1612.
  7. Zhuoru Wu, Nieng Yan, Liang Feng, Adam Oberstein, Hanchi Yan, Rosanna P. Baker, Lichuan Gu, Philip D. Jeffrey, Sinisa Urban, and Yigong Shi (2006). Structural analysis of a rhomboid family intramembrane protease reveals a gating mechanism for substrate entry. Nature Structural & Molecular Biology 13, 1084-1091. 2006 Nov 10; [Epub ahead of print].
 
蛋白去磷酸化酶领域:
  1. Yigong Shi (2009). Structure and Mechanism of Protein Serine/Threonine Phosphatases. Cell 139, 468-484.
  2. Yongna Xing, Zhu Li, Yu Chen, Philip D. Jeffery, and Yigong Shi (2008). Structural Mechanism of Demethylation and Inaction of Protein Phosphatase 2A. Cell 133, 154-163.
  3. Yu Chen, Yanhui Xu, Qing Bao, Yongna Xing, Zhu Li, Zheng Lin, Jeffry Stock, Philip P. Jeffrey, Yigong Shi (2007) Structural and biochemical insights into the regulation of protein phosphatase 2A by small t antigen of SV40. Nature Struct Mol Biol. 14(6), 527-34. Epub 2007 May 27.
  4. Yanhui Xu, Xing Yongna, Yu Chen, Yang Chao, Zheng Lin, Eugene Fan, Jong W. Yu, Stefan Strack, Philip D. Jeffrey, and Yigong Shi (2006). Structure of the Protein Phosphatase 2A Holoenzyme. Cell 127, 1239–1251.
  5. Xing Yongna, Yanhui Xu, Yu Chen, Philip D. Jeffrey, Yang Chao, Zheng Lin, Zhu Li, Stefan Strack, Jeffry B Stock, and Yigong Shi (2006). Structure of Protein Phosphatase 2A Bound to Tumor-inducing Toxins. Cell 127, 341-352.
  6. Yang Chao, Yongna Xing, Yu Chen, Yanhui Xu, Zheng Lin, Zhu Li, Philip D. Jeffrey, Jeffry B. Stock and Yigong Shi (2006). Structure and Mechanism of the Phosphotyrosyl Phosphatase Activator. Mol. Cell 23, 535-546.
 
蛋白降解与质量控制领域:
  1. Feng Wang, Ziqing Mei, Yutao Qi, Chuangye Yan, Siheng Xiang, Qi Hu, Jiawei Wang, and Yigong Shi. (2010) Structure and mechanism of the hexameric MecA-ClpC molecular machine. Nature,2011 Mar 2. [Epub ahead of print].
  2. Fan Zhang , Zhuoru Wu, Ping Zhang, Geng Tian, Daniel Finley, and Yigong Shi (2009). Mechanism of substrate unfolding and translocation by the regulatory particle of the proteasome from Methanocaldococcus jannaschii. Mol Cell 34, 485-496.
  3. Fan Zhang , Min Hu, Geng Tian, Ping Zhang, Daniel Finley, Philip D. Jeffrey, and Yigong Shi (2009). Structural insights into the regulatory particle of the proteasome from Methanocaldococcus jannaschii. Mol Cell 34, 473-484.
  4. Nieng Yan and Yigong Shi (2007). Allosteric Activation of a Bacterial Stress Sensor. Cell 131, 441-443.
  5. Min Hu, Lichuan Gu, Muyang Li, Philip D. Jeffrey, Wei Gu, and Yigong Shi (2006). Structural Basis of Competitive Recognition of p53 and MDM2 by HAUSP/USP7: Implications for the Regulation of the p53/MDM2 Pathway. PloS Biology 4, e27.
  6. Min Hu, Pingwei Li, Ling Song, Philip D. Jeffrey, Tatiana A. Chenova, Keith D. Wilkinson, Robert E. Cohen, and Yigong Shi (2005). Structure and mechanisms of the proteasome-associated deubiquitinating enzyme USP14. EMBO J. 24, 3747-3756. Epub 2005 Oct. 6.
  7. Min Hu, Pingwei Li, Muyang Li, Wenyu Li, Tingting Yao, Jia-Wei Wu, Wei Gu, Robert E. Cohen, and Yigong Shi (2002). Crystal Structure of a UBP-family Deubiquitinating Enzyme in Isolation and in Complex with Ubiquitin Aldehyde. Cell 111, 1041-1054.
 
SMAD蛋白信号转导领域 :
  1. Yigong Shi and Joan Massagué (2003). Mechanisms of TGF-b signaling from Cell Membrane to the Nucleus. (commissioned review article) Cell 113, 685-700.
  2. Jia-Wei Wu, Ariel R. Krawitz, Jijie Chai, Wenyu Li, Fangjiu Zhang, Kunxin Luo, and Yigong Shi (2002). Structural Mechanism of Smad4 Recognition by the Nuclear Oncoprotein Ski: Insight on Ski-Mediated Repression of TGF-b Signaling. Cell 111, 357-367.
  3. Jia-Wei Wu, Min Hu, Jijie Chai, Morgan Huse, Carey Li, Saw Kyin, Robert Fairman, Tom Muir, Joan Massagué, and Yigong Shi (2001). Crystal Structure of a Phosphorylated Smad2: Recognition of Phosphoserine Motif and Insights on Smad Function in TGF-b Signaling. Mol. Cell 8, 1277-1289.
  4. Geng Wu, Ye-Guang Chen, Barish Ozdamar, Cassie Gyuricza, P. Andrew Chong, Jeffrey L. Wrana, Joan Massagué, and Yigong Shi (2000). Structural Basis of Smad2 Recruitment by the Smad Anchor for Receptor Activation (SARA). Science 287, 92-97.
  5. Yigong Shi, Yan-Fei Wang, Lata Jayaraman, Haijuan Yang, Joan Massagué, and Nikola Pavletich (1998). Crystal Structure of A Smad MH1 Domain Bound to DNA: Insights on DNA-binding in TGF-b Signaling. Cell, 94, 585-594.
  6. Yigong Shi, Akiko Hata, Joan Massagué and Nikola P. Pavletich (1997) A structural basis for mutational inactivation of the tumour suppressor Smad4. Nature 388, 87-93.

 

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