颜宁　教授，博导
1996—2000 清华大学生物科学与技术系，学士
2000—2004 美国普林斯顿大学分子生物学系，博士
2005—2007 美国普林斯顿大学分子生物学系，博士后
2007-至今　 清华大学教授

主要科研领域与方向
人类基因组中编码蛋白的所有基因约有30%编码膜蛋白（membrane proteins）。膜蛋白在一切生命过程中起着关键作用，具有重要的生理功能。FDA批准上市的药物中,约50%的作用靶点为膜蛋白。因此，对膜蛋白结构与功能的研究具有极高的生物学意义及医药应用前景。但是由于研究手段有限，对膜蛋白的生物学功能以及结构研究极为困难。

转运蛋白（transport proteins）是膜蛋白的一大类，介导生物膜内外的化学物质以及信号交换。脂质双分子层在细胞或细胞器周围形成了一道疏水屏障， 将其与周围环境隔绝起来。尽管有一些小分子可以直接渗透通过膜，但是大部分的亲水性化合物，如糖，氨基酸，离子，药物等等，都需要特异的转运蛋白的帮助来通过疏水屏障。因此，转运蛋白在营养物质摄取，代谢产物释放以及信号转导等广泛的细胞活动中起着重要的作用。大量疾病都与膜转运蛋白功能失常有关，转运蛋白是诸如抗抑郁剂，抗酸剂等大量药物的直接靶点。

我们的研究兴趣主要集中在次级主动运输蛋白（secondary active transporters）的工作机理上。交替通路模型（alternating-access model）被用来解释转运蛋白的工作机理，在这个模型中，转运蛋白至少采取两种构象来进行底物的装载及卸载：一种向膜外开放，一种向膜内开放。有许多结构和生物物理学证据支持这个模型。但是，仍有两个最有趣的基本问题没有解决。第一,主动运输的能量偶联机制是什么？第二，在转运过程中，是什么因素触发了转运蛋白的构象变化？我们实验室使用基于结构的研究手段对次级主动运输蛋白进行研究，以期解决转运蛋白工作机理中的基本问题。

Publications

1. Sun L, Zeng X, Yan C, Sun X, Gong X, Rao Y, Yan N. Crystal structure of a bacterial homologue of glucose transporters GLUT1–4. Nature, 2012; 490:361–366.
2. Yin P, Deng D, Yan C, Pan X, Xi JJ, Yan N*, Shi Y*.Specific DNA-RNA Hybrid Recognition by TAL Effectors. Cell Rep. 2012; Sep 26. Epub ahead of print (co-corresponding authors)
3. Deng D, Yin P, Yan C, Pan X, Gong X, Qi S, Xie T, Mahfouz M, Zhu JK, Yan N*, Shi Y*. Recognition of methylated DNA by TAL effectors. Cell Res. 2012;22(10):1502-4. (co-corresponding authors)
4. Zhang X, Ren W, DeCaen P, Yan C, Tao X, Tang L, Wang J, Hasegawa K, Kumasaka T, He J, Wang J, Clapham DE, Yan N. Crystal structure of an orthologue of the NaChBac voltage-gated sodium channel. Nature. 2012;486(7401):130-4.
5. Tian Xie, Ruobing Ren, Yuan-yuan Zhang, Yuxuan Pang, Chuangye Yan, Xinqi Gong, Yuan He, Wenqi Li, Di Miao, Qi Hao, Haiteng Deng, Zhixin Wang, Jia-Wei Wu and Nieng Yan. Molecular Mechanism for Inhibition of a Critical Component in the Arabidopsis thaliana Abscisic Acid Signal Transduction Pathways, SnRK2.6, by Protein Phosphatase ABI1. J Biol Chem. 2012; 287:794-802.
6. Dong Deng, Chuangye Yan, Xiaojing Pan, Magdy Mahfouz, Jiawei Wang, Jian-Kang Zhu, Yigong Shi*, and Nieng Yan* Structural basis for the specific recognition of DNA by TAL effectors. Science. 2012; 335(6069):720-3, Epub: 2012 Jan 5. (* indicates corresponding authors).
7. Hao Q, Yin P, Li W, Wang L, Yan C, Lin Z, Wu JZ, Wang J, Yan SF, Yan N. The molecular basis of ABA-independent inhibition of PP2Cs by a subclass of PYL proteins.Mol Cell. 2011;42(5):662-72.
8. Lu F, Li S, Jiang Y, Jiang J, Fan H, Lu G, Deng D, Dang S, Zhang X, Wang J, Yan N. Structure and mechanism of the uracil transporter UraA. Nature. 2011;472(7342):243-6.
9. Dang S, Sun L, Huang Y, Lu F, Liu Y, Gong H, Wang J, Yan N. Structure of a fucose transporter in an outward-open conformation. Nature. 2010;467(7316):734-8.
10. Yuan X, Yin P, Hao Q, Yan C, Wang J, Yan N. Single amino acid alteration between valine and isoleucine determines the distinct pyrabactin selectivity by PYL1 and PYL2. J Biol Chem. 2010; 285(37):28953-8.
11. Hao Q, Yin P, Yan C, Yuan X, Li W, Zhang Z, Liu L, Wang J, Yan N. Functional mechanism of the abscisic acid agonist pyrabactin. J Biol Chem. 2010;285(37):28946-52.
12. Qi S, Pang Y, Hu Q, Liu Q, Li H, Zhou Y, He T, Liang Q, Liu Y, Yuan X, Luo G, Li H, Wang J, Yan N*,Shi Y*. Crystal structure of the Caenorhabditis elegans apoptosome reveals an octameric assembly of CED-4. Cell. 2010;141(3):446-57. (co-corresponding authors)
13. Wang Y, Huang Y, Wang J, Cheng C, Huang W, Lu P, Xu YN, Wang P, Yan N*, Shi Y*. Structure of the formate transporter FocA reveals a pentameric aquaporin-like channel. Nature. 2009;462(7272):467-72. (co-corresponding authors)
14. Yin P, Fan H, Hao Q, Yuan X, Wu D, Pang Y, Yan C, Li W, Wang J, Yan N. Structural insights into the mechanism of abscisic acid signaling by PYL proteins. Nat Struct Mol Biol. 2009;16(12):1230-6.
    Prior to 2007
15. Yan N, Shi Y. Allosteric activation of a bacterial stress sensor. Cell. 2007;131(3):441-3.
16. Wu Z*, Yan N*, Feng L*, Oberstein A, Yan H, Baker RP, Gu L, Jeffrey PD, Urban S, Shi Y. Structural analysis of a rhomboid family intramembrane protease reveals a gating mechanism for substrate entry.Nat Struct Mol Biol. 2006;13(12):1084-91.(co-first authors)
17. Yan N, Huh JR, Schirf V, Demeler B, Hay BA, Shi Y. Structure and activation mechanism of the Drosophila initiator caspase Dronc. J Biol Chem. 2006;281(13):8667-74.
18. Yan N, Xu Y, Shi Y. 2:1 Stoichiometry of the CED-4-CED-9 complex and the tetrameric CED-4: insights into the regulation of CED-3 activation. Cell Cycle. 2006;5(1):31-4.
19. Yan N, Shi Y. Mechanisms of apoptosis through structural biology. Annu Rev Cell Dev Biol. 2005; 21:35-56.
20. Yan N, Chai J, Lee ES, Gu L, Liu Q, He J, Wu JW, Kokel D, Li H, Hao Q, Xue D, Shi Y. Structure of the CED-4-CED-9 complex provides insights into programmed cell death in Caenorhabditis elegans. Nature. 2005; 437(7060):831-7.
21. Yan N, Gu L, Kokel D, Chai J, Li W, Han A, Chen L, Xue D, Shi Y. Structural, biochemical, and functional analyses of CED-9 recognition by the proapoptotic proteins EGL-1 and CED-4. Mol Cell. 2004; 15(6):999-1006.
22. Yan N, Wu JW, Chai J, Li W, Shi Y. Molecular mechanisms of DrICE inhibition by DIAP1 and removal of inhibition by Reaper, Hid and Grim. Nat Struct Mol Biol. 2004;11(5):420-8.
23. Yan N, Shi Y. Histone H1.2 as a trigger for apoptosis. Nat Struct Biol. 2003;10(12):983-5.
24. Chai J*, Yan N*, Huh JR, Wu JW, Li W, Hay BA, Shi Y. Molecular mechanism of Reaper-Grim-Hid-mediated suppression of DIAP1-dependent Dronc ubiquitination. Nat Struct Biol. 2003;10(11):892-8. (co-first authors)