Speaker：Sanduo Zheng, PhD, Harvard Medical School

Time: Friday, March 29st, 2019, 7:30 pm – 8:30 pm

Location: Karp Research Building 5th Floor, 1 Blackfan Cir, Boston, MA 02115

Registration: https://www.eventbrite.com/e/distinguished-scholar-club-at-harvard-medical-school-tickets-59364771630

膜蛋白在人体生理活动中扮演着非常重要的角色，是大部分临床药物的作用靶点。膜受体如G蛋白偶联受体可以将细胞外信号传递到细胞内,而膜转运蛋白可以介导离子或者分子的跨膜运输。我们实验室希望通过生物化学方法以及X射线晶体学、电子显微镜和核磁共振等结构手段研究膜受体信号转导的分子机制以及膜转运蛋白跨膜运输的分子机制。我们的长远目标是研发靶向膜蛋白的新型治疗药物。

Membrane proteinsplay important roles in virtually every aspect of human physiology and aretargets of most modern medicinal drugs. Membrane receptors such as G protein-coupledreceptors mediate cellular responses to a variety of extra cellular signals andmembrane transporters can move ions and molecules across the impermeable membrane. My lab aims to understand the molecular mechanism of membrane receptor signaling and membrane transport through biochemical and structural approaches including X-ray crystallography, electron microscopy and NMR, with a long-term goalto develop novel therapeutics targeting membrane proteins.

1.    Zheng S, Abreu N, Levitz J, Kruse AC*(2019). Structural basis for KCTD-mediated rapid desensitization of GABABsignaling. Nature. In press.

2.    Zheng S, Sham LT, Rubino FA, Brock KP, Robins WP, Mekalanos JJ, Marks DS, Bernhardt TG, Kruse AC*. (2018) Structural and mutagenic analysis of the lipid II flippase MurJ from Escherichia coli. Proc. Natl. Acad. Sci.U.S.A. 115 (26): 6709-6714

3.    ShamLT, Zheng S, Yakhnina AA, Kruse AC, Berhardt TG*. (2018) Loss of specificity variants of WzxC suggest thatsubstrate recognition is coupled with transporter opening in MOP-family flippase. Mol Microbiol.109 (5): 633-641

4.    HuangP#, Zheng S#, Wierbowski BM, Kim Y, Nedelcu D, Aravena L, Liu J, Kruse AC., Salic A*. (2018) The structural basis of smoothened activation in Hedgehog signaling. Cell 174: 1-13

5.    MaMahonC, Baier AS, Pascolutti R, Wegrecki M, Zheng S, Ong JX, Erlandson SC, Hilger D, Rasmussen SGF, Ring AM, Manglik A*, Kruse AC*. (2018) Yeastsurface display platform for rapid discovery of conformationally selective nanobodies. Nature Structural & Molecular Biology. 25: 289-296

6.    Zhou D#, Zhu X#, Zheng S, Tan D, Dong MQ, Ye K*. (2018) Cryo-EM structure of an early precursor oflarge ribosomal subunit reveals a half-assembled intermediate. Protein Cell. 10 (2): 120-130

7.    Sun Q#, Zhu X#, Qi J#, An W#, Lan P, Tan D, Chen R, Wang B, Zheng S, Zhang C, Chen X, Zhang W, Chen J, Dong M, Ye K*. (2017) Molecular architecture of the 90S small subunit pre-ribosome. eLife.6: e2208

8.    Li D, He W, Liu X, Zheng S, Qi Y, Li H, Mao F, Liu J, Sun Y, Pan L, Du K, Ye K, Li W*, Sui J*. (2017) A potent human neutralizing antibody Fc-dependently reduces established HBV infections. eLife. 6: e26738

9.    Schmidt HR#, Zheng S#, Gurpinar E, Koehl A, Manglik A., Kruse AC*. (2016) Crystal structure of humansigma1 receptor. Nature. 532: 527-530

10.  Shen M#, Zhang N#,Zheng S#, Zhang W, ZhangH, Lu Z, Su Q, Sun Y, Ye K, Li X*. (2016) Calmodulin in complex with the first IQ motif of myosin-5a functions as an intact calcium sensor. Proc. Natl. Acad. Sci. U.S.A. 113 (40)

11.  Zheng S#, Lan P#, Liu X,Ye K*. (2014) Interaction between Ribosome Assembly Factors Krr1 and Faf1 Is Essential for Formation of Small Ribosomal Subunit in Yeast. J Bio Chem.289: 22692-703

12.  Zheng S, Ye K*. (2014) Purification, crystallization and preliminary X-raydiffraction analysis of Imp3 in complex with an Mpp10 peptide involved in yeast ribosome biogenesis. Acta Crystallogr F Struct Biol Commun.70: 918-921

13.  Zheng S, Villa R, Wang J, FengY, Wang J, Becker PB, and Ye K*. (2014) Structural basis of X chromosome DNA recognition by MSL2CXC domain during dosage compensation in Drosophila. Genes & Development 28: 2652-2662

14.  Zheng S#, Wang J#, Feng Y#*, Wang J,Ye K*. (2012) Solution structure of MSL2 CXC domain reveals an unusual Zn3Cys9 clusterand similarity to pre-SET domains ofhistone lysine methyltransferases. PloS One. 7: e45437