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闫利明

清华大学亚博全站手机网页登录助理研究员

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研究冠状病毒RNA的转录复制,开发小分子药物

闫利明于2013年获得清华大学博士学位,至2016年在清华大学亚博全站手机网页登录从事博士后研究,目前任清华亚博全站手机网页登录助理研究员。闫利明博士长期开展冠状病毒感染和复制机制、病毒与宿主相互作用、以及相关的抗病毒药物研究工作,揭示冠状病毒病毒感染和复制的分子机制,研究宿主因子功能机制、宿主与病毒相互关系,发现抗病毒新机制和新手段,为冠状病毒防控和药物研发提供重要结构基础。在Science (2020)、Cell(2020, 2021)、Nature Communications (2020)和Nucleic Acids Research等杂志发表多项重要研究成果。

从事冠状病毒转录复制和抗病毒药物研发

闫利明博士主要研究冠状病毒RNA的转录复制。主要研究方向包括新型冠状病毒RNA复制、延伸、加帽和校正修复,利用结构生物和病毒学手段解析新结构和发现抗病毒新靶点,揭示新型冠状病毒RNA合成的精细过程。

闫利明博士致力于新型冠状病毒重要功能蛋白结构与分子作用机制研究,年来先后解析SARS冠状病毒基因组RNA校正复合物nsp10/nsp14、解旋酶nsp13、新型冠状病毒SARS-CoV-2复制转录复合体RTC和RTC的RNA延伸复合物等。率先在国际上成功解析新型冠状病毒最重要的药物靶点RNA聚合酶结构、RNA的延伸复合物和mRNA合成的第二步和第三步“帽子”合成的超级复合物近原子分辨率三维空间结构,揭示了病毒RNA的复制、延伸和mRNA加帽、基因组复制校正、逃逸核苷类抗病毒药物的分子机制。

1.L. Yan#, Y. Yang#, M. Li#, Y. Zhang#, L. Zheng#, J. Ge#, Y.C. Huang#, Z. Liu#, T. Wang, S. Gao, R. Zhang, Y.Y. Huang, L.W. Guddat, Y. Gao*, Z. Rao*, Z. Lou*, Coupling of N7-methyltransferase and 3'-5' exoribonuclease with SARS-CoV-2 polymerase reveals mechanisms for capping and proofreading, Cell, (2021).

2.L. Yan#, J. Ge#, L. Zheng#, Y. Zhang, Y. Gao, T. Wang, Y. Huang, Y. Yang, S. Gao, M. Li, Z. Liu, H. Wang, Y. Li, Y. Chen, L.W. Guddat, Q. Wang, Z. Rao*, Z. Lou*, Cryo-EM Structure of an Extended SARS-CoV-2 Replication and Transcription Complex Reveals an Intermediate State in Cap Synthesis, Cell, 184 (2021) 184-193 e110.

3.L. Yan#, Y. Zhang#, J. Ge, L. Zheng, Y. Gao, T. Wang, Z. Jia, H. Wang, Y. Huang, M. Li, Q. Wang, Z. Rao*, Z. Lou*, Architecture of a SARS-CoV-2 mini replication and transcription complex, Nat Commun, 11 (2020) 5874.

4.L.M. Yan#, Y.B. Qi#, X.F. Huang#, C.T. Yu#, L. Lan, X.Y. Guo, Z.H. Rao, J.J. Hu*, Z.Y. Lou*, Structural basis for GTP hydrolysis and conformational change of MFN1 in mediating membrane fusion, Nature structural & molecular biology, 25 (2018) 233-+.

5.L. Yan#, Y. Qi#, D. Ricketson#, L. Li, K. Subramanian, J. Zhao, C. Yu, L. Wu, R. Sarsam, M. Wong, Z. Lou, Z. Rao*, J. Nunnari*, J. Hu*, Structural analysis of a trimeric assembly of the mitochondrial dynamin-like GTPase Mgm1, Proceedings of the National Academy of Sciences of the United States of America, 117 (2020) 4061-4070.

6.L. Yan#, S. Sun#, W. Wang, J. Shi, X. Hu, S. Wang, D. Su, Z. Rao, J. Hu*, Z. Lou*, Structures of the yeast dynamin-like GTPase Sey1p provide insight into homotypic ER fusion, J Cell Biol, 210 (2015) 961-972.

7.L. Yan#, Y. Ma#, D. Liu#, X. Wei, Y. Sun, X. Chen, H. Zhao, J. Zhou, Z. Wang*, W. Shui*, Z. Lou*, Structural basis for the impact of phosphorylation on the activation of plant receptor-like kinase BAK1, Cell Res, 22 (2012) 1304-1308.

8.L. Yan#, Y. Ma#, Y. Sun, J. Gao, X. Chen, J. Liu, C. Wang, Z. Rao*, Z. Lou*, Structural basis for mechanochemical role of Arabidopsis thaliana dynamin-related protein in membrane fission, J Mol Cell Biol, 3 (2011) 378-381.

9.J. Wang#, L. Li#, Z. Ming, L. Wu, L. Yan*, Crystal Structure of the Epo1-Bem3 Complex for Bud Growth, Int J Mol Sci, 22 (2021).

10.Y. Gao#, L. Yan#, Y. Huang#, F. Liu#, Y. Zhao, L. Cao, T. Wang, Q. Sun, Z. Ming, L. Zhang, J. Ge, L. Zheng, Y. Zhang, H. Wang, Y. Zhu, C. Zhu, T. Hu, T. Hua, B. Zhang, X. Yang, J. Li, H. Yang, Z. Liu, W. Xu, L.W. Guddat, Q. Wang*, Z. Lou*, Z. Rao*, Structure of the RNA-dependent RNA polymerase from COVID-19 virus, Science, 368 (2020) 779-782.

11.R.F. Yao#, Z.H. Ming#, L.M. Yan#, S.H. Li#, F. Wang, S. Ma, C.T. Yu, M. Yang, L. Chen, L.H. Chen, Y.W. Li, C. Yan, D. Miao, Z.Y. Sun, J.B. Yan, Y.N. Sun, L. Wang, J.F. Chu, S.L. Fan, W. He, H.T. Deng, F.J. Nan, J.Y. Li, Z.H. Rao*, Z.Y. Lou*, D.X. Xie*, DWARF14 is a non-canonical hormone receptor for strigolactone, Nature, 536 (2016) 469-+.

12.Z. Jia#, L. Yan#, Z. Ren, L. Wu, J. Wang, J. Guo, L. Zheng, Z. Ming, L. Zhang, Z. Lou, Z. Rao*, Delicate structural coordination of the Severe Acute Respiratory Syndrome coronavirus Nsp13 upon ATP hydrolysis, Nucleic acids research, 47 (2019) 6538-6550.

13.Y. Qi#, L. Yan#, C. Yu#, X. Guo, X. Zhou, X. Hu, X. Huang, Z. Rao*, Z. Lou*, J. Hu*, Structures of human mitofusin 1 provide insight into mitochondrial tethering, J Cell Biol, 215 (2016) 621-629.

14.C. Yu#, J. Zhao#, L. Yan#, Y. Qi, X. Guo, Z. Lou, J. Hu*, Z. Rao, Structural insights into G domain dimerization and pathogenic mutation of OPA1, J Cell Biol, 219 (2020).

15.Z. Ming#, W. Wang#, Y. Xie, P. Ding, Y. Chen, D. Jin, Y. Sun, B. Xia, L. Yan*, Z. Lou*, Crystal structure of the novel di-nucleotide cyclase from Vibrio cholerae (DncV) responsible for synthesizing a hybrid cyclic GMP-AMP, Cell Res, 24 (2014) 1270-1273.

16.Z. Ren#, L. Yan#, N. Zhang, Y. Guo, C. Yang, Z. Lou, Z. Rao*, The newly emerged SARS-like coronavirus HCoV-EMC also has an "Achilles' heel": current effective inhibitor targeting a 3C-like protease, Protein Cell, 4 (2013) 248-250.

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