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个人信息

博士生导师
研究员
 
Email: pengzhang01@sibs.ac.cn
个人网页: http://pzhangxtal.sippe.ac.cn

研究方向

结构生物学

张鹏

个人简介

1998.9-2002.7 本科 山东大学生物化学与分子生物学系
2002.9-2007.12
博士 中科院生物化学与细胞生物学研究所
2008.2-2010.10
博士后 美国普林斯顿大学分子生物学系
2010.10-
现在 研究员 中科院上海生科院植物生理生态研究所

曾入选上海市浦江人才2011),上海生科院“S人才(2012,终评优秀),国家基金委优秀青年基金(2013),上海市首届青年拔尖人才(2015)。承担科技部、基金委、中科院、上海市及英国皇家学会多项科研项目,科技部青年973项目首席科学家。担任中国生物物理学会理事,上海市生物物理学会常务理事。研究成果以通讯作者发表在NatureNature PlantsCell ResPNASNat CommunEMBO RepMol Plant等国际期刊上

研究工作

研究组利用结构生物学、生物化学及遗传学方法,研究生物体活性小分子代谢物合成、跨膜转运与信号传递的分子机理。

1) 活性小分子跨膜转运的分子机理:跨细胞膜的物质转运是细胞与内外环境之间进行物质交流的主要方式,与生命体的生长发育和环境响应等密切相关。探索活性小分子跨膜转运的分子机理是我们的研究兴趣之一。ECFABC转运蛋白是微生物与植物中存在的一大类B族维生素转运蛋白,生理功能重要。我们解析了跨膜转运叶酸(B9)、泛酸(B5)、钴离子(合成B12)等ECF转运蛋白的三维结构,揭示了底物识别和跨膜转运的分子过程,提出了ECFABC转运蛋白的工作模型(Nature, 2013; PNAS, 2014; Nature Commun2015Cell Res, 2017; Trends Microbiol, 2013.)。在另一工作中,我们解析了蓝藻CO2浓缩机制(CCM)中HCO3-跨膜转运蛋白BicA结合底物HCO3-的三维结构,揭示了HCO3-跨膜转运的分子机理,阐释了人体同源的HCO3-转运蛋白突变致病的分子机理,并为CCM在高等植物中的应用提供了分子基础(Nature Plants, 2019)。

2)活性小分子介导的跨膜信号传递机理:跨细胞膜的信号传递是细胞与内外环境间进行信息交流的主要方式,许多活性小分子在跨膜信号传递中发挥着重要功能。我们的另一研究兴趣是探究活性小分子物质介导的跨膜信号传递机理。我们的研究揭示了细菌细胞膜双组分信号复合体XylFII-LytS结合木糖分子,调控木糖跨膜转运、代谢的分子机制(PNAS, 2017a);阐明了真核生物线粒体膜间隙Ups1-Mdm35复合体特异结合并跨膜间隙转运磷脂酸,受心磷脂分子反馈调控的分子机理 (EMBO Rep, 2015) ;解析了植物磷脂酶D结合底物前后不同状态的结构,阐明了真核生物磷脂酸生成的催化和调控机制、抑制剂的作用机理(Cell Res, 2019)

3)重要活性小分子的合成机理解析与分子设计:研究植物体产生的活性代谢物,如:紫杉醇、叶绿素等萜类及衍生物的合成过程、酶催化机理,基于蛋白结构与机理开展合成生物学途径设计。前期研究中揭示了萜类活性化合物合成效率及特异性的分子机理(Mol Plant. 2016Biochem J. 2013PNAS, 2017b; Plant Communications, 2019);阐明了利福平(治疗结核病一线药物)磷酸转移酶磷酸化利福平致其失活的分子机制(PNAS, 2016)。


主要成果

 

    1. Liu Z.F.#, Li J.X.#, Sun Y.W., Zhang P.*, Wang Y.*. Structural insights into the catalytic mechanism of a plant diterpene glycosyltransferase SrUGT76G1. Plant Communications. 2020 1(1), 100004. doi: 10.1016/j.xplc.2019.100004.

    2. Li J.X.#, Yu F. #, Guo H., Xiong R.X., Zhang W.J., He F.Y., Zhang M.H., Zhang P.*. Crystal structure of plant PLDα1 reveals catalytic and regulatory mechanisms of eukaryotic phospholipase D. Cell Res. 2019 (doi.org/10.1038/s41422-019-0244-6).

    3. Wang C.C., Sun B., Zhang X., Huang X.W., Zhang M.H., Guo H., Chen X., Huang F., Chen T.Y., Mi H.L., Yu F., Liu L.N., Zhang P.*. Structural mechanism of the active bicarbonate transporter from cyanobacteria. Nature Plants. 2019. 5,1184-1193.

    4. He J, Zhang C, Dai H, Liu H, Zhang X, Yang J, Chen X, Zhu Y, Wang D, Qi X, Li W, Wang Z, An G, Yu N, He Z, Wang YF, Xiao Y, Zhang P, Wang E. A LysM receptor heteromer mediates perception of arbuscular mycorrhizal symbiotic signal in rice. Mol Plant. 2019. doi: 10.1016/j.molp.2019.10.015.

    5. Sun Y.W., Chen Z., Li J.X., Li .J.H., Lv H.J., Yang J.Y., Li W.W., Xie D.A., Xiong Z.Q., Zhang P., Wang Y.*. Diterpenoid UDP-glycosyltransferases from Chinese Sweet Tea and Ashitaba Complete the Biosynthesis of Rubusoside. Mol Plant. 2018. doi.10.1016/j.molp.2018.05.010

    6. Yang Y, Liang T, Zhang L, Shao K, Gu X, Shang R, Shi N, Li X, Zhang P, Liu H.*. UVR8 interacts with WRKY36 to regulate HY5 transcription and hypocotyl elongation in Arabidopsis. Nature Plants. 2018. 4:98-107

    7. Li J.X. #, Wang C.Y. # , Yang G.H., Sun Z., Guo H., Shao K., Gu Y., Jiang W.H.*, Zhang P.*. Molecular mechanism of environmental D-xylose perception by a XylFII-LytS complex in bacteria. Proc Natl Acad Sci U S A. 2017. 114(31):8235-8240. 

    8. Fang X.,Li J.X.,Huang J.Q.,Xiao Y.L.,Zhang P.,Chen X.Y.*. Systematic identification of functional residues of Artemisia annua amorpha-4,11- dienesynthase.  Biochem J. 2017. 474(13):2191-2202.

    9. Zhou F. #, Wang C.Y. # , Gutensohn M. #, Jiang L, Zhang P., Zhang D.B., Dudareva N.*, Lu S.*. A Novel Recruiting Protein of Geranylgeranyl Diphosphate Synthase Controls Metabolic Flux towards Chlorophyll Biosynthesis in Rice. Proc Natl Acad Sci U S A. 2017. 114(26):6866-6871.

    10. Bao Z.H. #, Qi X.F. #, Hong S., Xu K., He F.Y., Zhang M.H., Chen J.G., Chao D.Y., Zhao W., Li D.F., Wang J.W. *, Zhang P.*. Structure and mechanism of a group‐I cobalt energy coupling factor transporter. Cell Res. 2017. 27(5):675-687. 

    11. Qi X.F., Lin W., Ma M.L., Wang C.Y., He Y., He N.S., Gao J., Zhou H., Xiao Y.L., Wang Y., and Zhang P.*. Structural basis of rifampin inactivation by rifampin phosphotransferase. Proc Natl Acad Sci U S A. 2016. 113(14):3803-3808.

    12. Wang C. #, Chen Q. #, Fan D., Li J., Wang G.*, and Zhang P.*. Structural analyses of short-chain prenyltransferases identify an evolutionarily conserved GFPPS clade in Brassicaceae plants. Mol Plant. 2016. 9:195–204. (Cover & Highlight)

    13. Zhao Q. #, Wang C.C. #, Wang C.Y., Guo H., Bao Z.H., Zhang M.H., Zhang P. *. Structures of FolT at substrate-bound and substrate-released conformations reveal a gating mechanism of ECF transporters. Nat Commun. 2015. 6:7661.

    14. Yu F. #, He F.Y. #, Yao H.Y., Wang C.Y., Wang J.C., Li J.X., Qi X.F., Xue H.W.*, Ding J.P.*, Zhang P.*. Structural basis of intramitochondrial phosphatidic acid transport mediated by Ups1-Mdm35 complex. EMBO Rep. 2015. 16 (7). 813-23. (Recommended by Faculty 1000, Biology)

    15. Li X.M., Chao D.Y., Wu Y., Huang X.H., Chen K., Cui L.G., Su L., Ye W.W., Chen H., Chen H.C., Dong N.Q., Guo T., Shi M., Feng Q., Zhang P., Han B., Shan J.X.*, Gao J.P.*, Lin H.X.*. Natural alleles of a proteasome α2 subunit gene contribute to thermotolerance and adaptation of African rice. Nat Genet.  2015. 47(7):827-33.

    16. Zhang M.H.#, Bao Z.H.#, Zhao Q., Guo H., Xu K., Wang C.C., Zhang P.*. Structure of a pantothenate transporter and implications for ECF module sharing and energy coupling of group II ECF transporters. Proc Natl Acad Sci U S A. 2014. 111(52):18560-5.

    17. Yang X., Ren W.Q., Zhao Q.X., Zhang P, Wu F.J., He Y.K.*.  Homodimerization of HYL1 ensures the correct selection of cleavage sites in primary miRNA. Nucleic Acids Res. 2014. 42(19):12224-12236.

    18. Zhang Z.L., Wu J., Lin W., Wang J., Yan H., Zhao W., Ma J., Ding J.P.*, Zhang P.*., and Zhao G.P.*. Subdomain II of alpha-isopropylmalate synthase is essential for activity: Inferring a mechanism of feedback inhibition. J Biol Chem. 2014. 289(40): 27966-27978.

    19. Lin W., Wang Y., Han X.B., Zhang Z.L.,Wang C.Y., Wang J., Yang H.Y., Lu Y.H., Jiang W.H., Zhao G.P.*., Zhang P.*. Atypical OmpR/PhoB subfamily response regulator GlnR of actinomycetes functions as a homodimer, stabilized by the unphosphorylated conserved Asp-focused charge. J Biol Chem. 2014. 289(22): 15413-15425.

    20. Zhang P.*. Structure and mechanism of energy-coupling factor transporters. Trends Microbiol. 2013. 21(12):652-9. Invited review

    21. Xu K. #, Zhang M.H. #, Zhao Q. #, Yu F. #, Guo H., Wang C.Y., He F.Y., Ding J.P., Zhang P.*. Crystal structure of a folate energy-coupling factor transporter from Lactobacillus brevis. Nature. 2013. 497(7448):268-71. (Recommended by Faculty 1000, Biology; Highlighted by Nature China.)

    22. Li J.X. #, Fang X. #, Zhao Q., Ruan J.X., Yang C.Q., Wang L.J., Miller D.J., Faraldos J.A., Allemann R.K., Chen X.Y.*, Zhang P.*. Rational engineering of plasticity residues of sesiquiterpene synthases from Artemisia annua: product specificity and catalytic efficiency.  Biochem J. 2013. 451(3):417-26.

    23. Zhang P., Wang J.W. and Shi Y.*. Structure and mechanism of the S component of a bacterial ECF transporter. Nature. 2010; 468(7324): 717-720. (Recommended by Faculty 1000, Biology)

    24. Zhang P.#, Ma J.#, Zhang Z., Zha M., Xu H., Zhao G., Ding J.*. Molecular basis of the inhibitor selectivity and insights into the feedback inhibition mechanism of citramalate synthase from Leptospira interrogans. Biochem J. 2009; 421:133-43.

    25. Ma J.#, Zhang P.#, Zhang Z.L., Zha M.W., Xu H., Zhao G..P., and Ding J.*. Molecular basis of the substrate specificity and the catalytic mechanism of citramalate synthase from Leptospira interrogans. Biochem J. 2008; 415:45-56.

    26. Zhang P., Zhao J., Wang B., Du J., Lu Y., Chen J. and Ding J.*. The MRG domain of human MRG15 uses a shallow hydrophobic pocket to interact with the N-terminal region of PAM14. Protein Sci. 2006; 15:2423-34.

    27. Zhang P.#, Du J.#, Sun B., Dong X., Xu G.., Zhou J., Huang Q., Liu Q., Hao Q. and Ding J.*. Structure of human MRG15 chromo domain and its binding to Lys36-methylated histone H3. Nucleic Acids Res. 2006; 34:6621-8.

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