鄭三多博士 研究員

Sanduo Zheng, Ph.D.

Assistant Investigator, NIBS, Beijing

Phone：010-80726688-8565

E-mail：zhengsanduo@nibs.ac.cn

教育經歷 Education

2013年 北京生命科學研究所與北京師范大學聯合培養結構生物學博士

Ph.D. in Structural Biology,

National Institute of Biological Science (NIBS), Beijing & Beijing Normal University, Beijing, China.

2008年 蘭州大學生物學基地班學士

B.S., Biological Science,

Lanzhou University, Lanzhou, China

工作經歷 Professional Experience

研究概述 Research Description

膜蛋白在人體生理活動中扮演著非常重要的角色，是大部分臨床藥物的作用靶點。膜受體如G蛋白偶聯受體可以將細胞外信號傳遞到細胞內,而膜轉運蛋白可以介導離子或者分子的跨膜運輸。我們實驗室希望通過生物化學方法以及X射線晶體學、電子顯微鏡和核磁共振等結構手段研究膜受體信號轉導的分子機制以及膜轉運蛋白跨膜運輸的分子機制。我們的長遠目標是研發靶向膜蛋白的新型治療藥物。

Membrane proteins play important roles in virtually every aspect of human physiology and are targets of most modern medicinal drugs. Membrane receptors such as G protein-coupled receptors mediate cellular responses to a variety of extracellular signals and membrane 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 goal to develop novel therapeutics targeting membrane proteins.

代表文章 Representative Publications (#共同一作，*通訊作者)

1. Nie Y^#, Qiu Z^#, Chen Z, Song X, Ma Y, Cyster JG, Zheng S* (2023). Specific binding of GPR174 by endogenous lysophosphatidylserine leads to high constitutive Gs signaling. Nature Communications 14 (1).

2. Jiang W^#, Wang W^#, Kong Y, Zheng S* (2023). Structural basis for the ubiquitination of G protein βγ subunits by KCTD5/Cullin3 E3 ligase. Science Advances 9 (28).

3. Yang J, Chen P, Cao Y, Liu S, Wang W, Li L, Li J, Jiang Z, Ma Y, Chen S, Zheng S, Qi X*, Jiang H*(2023). Chemical inhibition of mitochondrial fission via targeting the DRP1-receptor interaction. Cell Chemical Biology 30 (3).

4. Wang Q^#, Meng F^#, Xie Y, Wang W, Meng Y, Li L, Liu T, Qi J, Ni X, Zheng S, Huang J*, Huang N*(2023). In Silico Discovery of Small Molecule Modulators Targeting the Achilles’ Heel of SARS-CoV-2 Spike Protein. ACS central science 9 (2).

5. Chen S, Teng X, Zheng S* (2023). Molecular basis for the selective G protein signaling of somatostatin receptors. Nature Chemical Biology 19 (2): 133-140.

6. Li Y^#, Liu J^#, Chen W^#, Wang W, Yang F, Liu X, Sheng Y, Du K, He M, Lyu X, Li H, Zhao L, Wei Z, Wang F, Zheng S, Sui J*(2023). A pH-dependent anti-CD47 antibody that selectively targets solid tumors and improves therapeutic efficacy and safety. Journal of Hematology & Oncology 16 (1).

7. Jiang W, Zheng S* (2022). Structural insights into the galanin receptors signaling. Proc. Natl. Acad. Sci. U.S.A 119 (21).

8. Teng X^#, Chen S^#, Wang Q, Chen Z, Wang X, Huang N, Zheng S* (2022). Structural insights into G protein activation by D1 dopamine receptor. Science Advances 8 (23)

9. Teng X, Chen S, Nie Y, Zheng S* (2022). Ligand recognition and biased agonism of the D1 dopamine receptor. Nature communications 13 (1), 1-11.

10. Ma J^#, Su D^#, Sun Y, Huang X, Liang Y, Fang L, Ma Y, Li W, Liang P*, Zheng S* (2021). Cryo-electron microscopy structure of S-trimer, a subunit vaccine candidate for COVID-19. Journal of Virology 95 (11).

11. Pascolutti R, Erlandson SC, Burri DJ, Zheng S, Kruse AC* (2020). Mapping and engineering the interaction between adiponectin and T-cadherin. J Bio Chem 295 (9), 2749-2759

12. Sjodt M, Rohs PD, Gilman MS, Erlandson SC, Zheng S, Green AG, Brock KP, Taguchi A, Kahne D, Walker S, Marks D, Rudner DZ, Bernhardt TG, Kruse AC* (2020). Structural coordination of polymerization and crosslinking by a SEDS-bPBP peptidoglycan synthase complex. Nature Microbiology 5 (6), 813-820

13. Liu H, Zheng S, Hou X, Liu X, Du K, Lv X, Li Y, Yang F, Li W, Sui J* (2020). Novel Abs targeting the N-terminus of fibroblast growth factor 19 inhibit hepatocellular carcinoma growth without bile-acid-related side-effects. Cancer science 111 (5), 1750-1760

14. Zheng S, Abreu N, Levitz J, Kruse AC* (2019). Structural basis for KCTD-mediated rapid desensitization of GABA_B signaling. Nature 567: (127-131).

15. 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

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

17. Huang P^#, 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

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

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

20. 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

21. 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

22. Schmidt HR^#, Zheng S^#, Gurpinar E, Koehl A, Manglik A., Kruse AC*. (2016) Crystal structure of human sigma1 receptor. Nature 532: 527-530

23. Shen M^#, Zhang N^#, Zheng S^#, Zhang W, Zhang H, 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)

24. 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

25. Zheng S, Villa R, Wang J, Feng Y, Wang J, Becker PB, and Ye K*. (2014) Structural basis of X chromosome DNA recognition by MSL2 CXC domain during dosage compensation in Drosophila. Genes & Development 28: 2652-2662

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

Invited reviews and comments

1. Zheng S, Kruse AC*. (2019) Ion Channels: Solving a specificity mystery. eLife

2. Alon A^#, Schmidt H^#, Zheng S^#, Kruse AC*. (2017) Structure perspectives on Sigma-1 receptor function. Adv Exp Med Biol. 964:5-13