Full time faculty

Adjunct professor

Chair professor

Administration

Ning Yan

Ning Yan, PhD.

Professor

1996-2000 B.S., Department of Biology, Tsinghua University
2000-2004 Ph.D., Department of Molecular Biology, Princeton University
2005-2007 Postdoc, Department of Molecular Biology, Princeton University
2007 Professor, School of medicine, Tsinghua University

Research Interest

It is estimated that approximately 30% of the coding genes in human genome are for integral membrane proteins, which play an essential role in multi-processes of all kinds of life forms. Membrane proteins also constitute the major drug targets. Approximately 50% of the FDA-approved drugs target membrane proteins. Therefore, information on the structure and mechanism of membrane proteins is invaluable to both biological understanding and potential medical application. Unfortunately, due to the daunting technical challenges, it has been extremely difficult to conduct biochemical and structural studies on membrane protein.

Transport proteins constitute a major class of membrane proteins that mediate the exchange of chemicals and signals across the biological membrane. The lipid bilayer sets a hydrophobic barrier that insulates the cellular or organelle contents from the environment. Although some low molecular weight chemicals can be permeated directly through membrane, most of the hydrophilic chemicals, such as sugars, amino acids, ions, drugs, etc, require specific transport proteins to traffic through the hydrophobic wall. Therefore, transport proteins play an essential role in a broad spectrum of cellular activities, such as uptake of nutrients, release of metabolites, and signal transductions. A large number of diseases are correlated with the malfunction of membrane transporters. Transport proteins are direct targets of widely prescribed drugs such as antidepressants and heartburn relief.

We are particularly interested in the functional mechanism of the secondary active transporters. An alternating-access model was proposed to account for a general mechanism of transporter proteins. In this model, to upload and download substrate, a transporter protein adopts at least two conformations: one exclusively open to the outside and the other to the inside of the membrane. This model was supported by several lines of structural and biophysical evidence. Nevertheless, there are two most interesting and general questions yet to be addressed. First, what is the energy coupling mechanism for the active transporters? Second, what triggers the obligatory conformational change of the transporter during the transport cycle? In order to address these fundamental questions in the mechanistic understanding of the transporter proteins, my lab launched structure-based investigations of the secondary active transporters.

Publications

  1. 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.
  2. 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).
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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)
  9. 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)
  10. 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
  11. Yan N, Shi Y. Allosteric activation of a bacterial stress sensor. Cell. 2007;131(3):441-3.
  12. 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)
  13. 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.
  14. 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.
  15. Yan N, Shi Y. Mechanisms of apoptosis through structural biology. Annu Rev Cell Dev Biol. 2005; 21:35-56.
  16. 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.
  17. 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.
  18. 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.
  19. Yan N, Shi Y. Histone H1.2 as a trigger for apoptosis. Nat Struct Biol. 2003;10(12):983-5.
  20. 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)

Address: School of Medicine, Tsinghua University, Beijing, China. 100084
TEL : 86-10-62796067
E-mail: structure@tsinghua.edu.cn



Tsinghua University,Beijing,China,100084
Tel:+86-10-62772269  Fax:+86-10-62788604  Email:swxrs@tsinghua.edu.cn