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Nieng YAN


 Nieng YAN





Research Area:
Transport proteins constitute a major class of membrane proteins that mediate the exchange of chemicals and signals across the biological membrane, which 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.

Selected Publications:

1.Zhang X, DeCaen P, Clapham D, Xia M, Li Y, Liu H, Jiang X, Ren W, Wu J, Yu F, Huang S, He J, Yan N, and Gong H. Analysis of the selectivity filter of the voltage-gated sodium channel NavRh. CELL RESEARCH 23:409-422. 2012

2.Zhang X, Yan N. The conformational shifts of the voltage sensing domains between NavRh and NavAb. CELL RESEARCH 23:444-447 2012

3.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 490:361-366. 2012

4.Yin P, Deng D, Yan C, Pan X, Xi J, Yan N, Shi Y. Specific DNA-RNA hybrid recognition by TAL effectors. CELL REPORTS 2:707-713. 2012

5.Deng D, Yin P, Yan C, Pan X, Gong X, Qi S, Xie T, Mahfouz M, Zhu J, Yan N*, Shi Y*. Recognition of methlyated DNA by TAL effectors. CELL RESEARCH 22:1502-1504. 2012 (* indicates corresponding authors)

6.Sugihara J, Sun L, Yan N, Kabacka H. Dynamics of the L-fucose/H+ symporter revealed by fluorescence spectroscopy. PNAS, 109:14847-14851 2012

7.Zhang X, Ren W, DeCaen P, Yan C, Tao X, Tang L, Wang J, Hasegawa K, Kumasaka T, He J, Wang J, Clapham D., Yan N. Crystal structure of an orthologue of the NaChBac voltage-gated sodium channel. NATURE 486: 130-134 2012

8.Deng D, Yan C, Pan X, Mahfouz M, Wang J, Zhu J, Shi Y*, Yan N*. Structural basis for the specific recognition of DNA by TAL effectors. SCIENCE 335: 720-723 2012 (* indicates corresponding authors)

9.Xie T, Ren R, Zhang Y, Pang Y, Yan C, Gong X, He Y, Li W, Miao D, Hao Q, Deng H, Wang Z, Wu J*, Yan N*. Molecular mechanism for the inhibition of a critical component in the Arabidopsis thaliana abscisic acid signal transduction pathways, SnRK2.6, by the protein phosphatase ABI1. J BIOL. CHEM 287: 794-802 2012 (* indicates corresponding authors)

10.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. 

11.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. 

12.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. 

13.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. 

14.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. 

15.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) 

16.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) 

17.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 

18.Yan N, Shi Y. Allosteric activation of a bacterial stress sensor. Cell. 2007;131(3):441-3. 

19.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) 

20.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. 

21.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. 

22.Yan N, Shi Y. Mechanisms of apoptosis through structural biology. Annu Rev Cell Dev Biol. 2005; 21:35-56. 

23.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. 

24.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. 

25.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. 

26.Yan N, Shi Y. Histone H1.2 as a trigger for apoptosis. Nat Struct Biol. 2003;10(12):983-5. 

27.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) .




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