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傅青山

姓名:傅青山 性别: 职称:研究员 学历:博士 电话:(0760)85281627 电子邮件:fuqingshan@simm.ac.cn 职务:课题组长 通讯地址:广东翠亨新区中瑞(欧)工业园健康医药示范区

  • 个人简历

    傅青山,博士,研究员,课题组长,博士研究生导师。2002年毕业于山东师范大学,获得生物科学学士学位。2005年在张红雨老师指导下获得生物信息学硕士学位。2006年加入中国科学院生物化学与分子生物学研究所,在胡红雨老师指导下进行蛋白质积聚和泛素介导的蛋白质降解相关的研究,于2010年6月毕业,获得博士学位。2011年1月-2018年12月,在哈佛大学医学院James Chou研究组进行博士后研究,利用液态核磁共振技术解析了第一个TNFR家族跨膜三聚体的结构,解析了HIV包膜蛋白跨膜区,以及临近跨膜保守区的结构。2019年1月-2021年8月,在哈佛大学医学院任讲师职位,继续进行HIV包膜蛋白以及SARS-COV2刺突蛋白跨膜结构的研究,并基于临近跨膜保守区的结构进行药物筛选,取得了优异的成果。现为上海药物研究所研究员,中山药物创新研究院研究员、课题组长。

  • 研究领域

    核磁共振,膜蛋白结构,抗病毒药理研究;寿命与神经内分泌以及代谢的调控机制。

  • 研究成果

    傅青山研究员在膜蛋白结构、生物膜动力学、生物膜的纳米颗粒组装和膜感受器的信号跨膜传递等领域做了大量的工作。细胞膜受体跨膜结构域具有较强的疏水性和动态性,难以应用X射线晶体衍射和冷冻电镜(Cryo-EM)进行研究。因此,受体跨膜区成为细胞信号跨膜传递研究中的盲区。利用液态核磁共振(NMR)技术,结合生物化学与膜生物学技术,发展了研究蛋白质跨膜区结构及其动态变化的新方法(Fu, et al, Nature Protocols, 2019)。利用该方法,首次解析了细胞死亡受体(death receptor, TNFR family)在生物膜中同源三聚体的跨膜结构域,揭示了细胞死亡受体集簇装配的信号传递机制(Fu Q, et al, Molecular Cell, 2016);首次解析了HIV-1包膜蛋白的跨膜结构域及其临近保守区在生物膜中的定位和动态变化,为艾滋病病毒(HIV)侵染细胞过程中膜融合机制的研究奠定了基础(Fu Q, et al, PNAS, 2018; Dev J, Park D, Fu Q, et al, Science, 2016)。 在Science , Cell, Mol. Cell, Nat. Protoc., PNAS, Nat. Commun.等国际权威期刊上发表论文20余篇。研究成果得到了国内外同行的关注与认可,多次被J. Am. Chem. Soc.,Angew. Chem. Int. Ed. 等期刊正面评述,并被哈佛大学、中科院网站等进行专题报道。2017年获得了Merck-Harvard基金的研究资助,独立承担了研究项目:“艾滋病病毒包膜蛋白MPER保守区的结构和药物研究”,为艾滋病病毒疫苗的研究提供了新的保守抗原。

  • 代表性论著(*:通讯作者)

    1. Fu Q, Chou JJ*. (2021) A trimeric hydrophobic zipper mediates the intramembrane assembly of SARS-CoV-2 spike. J Am Chem Soc. 143(23),8543-8546. PMID:34086443.

    2. Piai A#, Fu Q#, Sharp AK#, Bighi B, Brown AM*, Chou JJ*. (2021) NMR Model of the Entire Membrane-Interacting Region of the HIV-1 Fusion Protein and Its Perturbation of Membrane Morphology. J Am Chem Soc. 143(17), 6609-6615.

    3. Fu Q#, Piai A#, Chen W#, Xia K, Chou JJ*. (2019). Structure Determination Protocol for Transmembrane Domain Oligomers. Nature Protocols 14, 2483-2520. PMID:31270510

    4. Fu Q#, Shaik MM#, Cai Y, Ghantous F, Piai A, Peng H, Rits-Volloch S, Liu Z, Harrison SC*, Seaman MS, Chen B*, Chou JJ*.  (2018).Structure of the membrane proximal external region of HIV-1 envelope glycoprotein. Proc Natl Acad Sci USA, 115(38):E8892-E8899 PMID:30185554

    5. Fu Q#, Fu T#, Cruz AC, Sengupta P, Thomas SK, Wang S, Siegel RM, Wu H*, Chou JJ*. (2016). Structural Basis and Functional Role of Intramembrane Trimerization of the Fas/CD95 Death Receptor. Molecular Cell, 61(4):602-613 PMCID: PMC4761300

    6. Piai A#, Fu Q#, Cai Y, Ghantous F, Xiao T, Shaik M, Peng H, Rits-Volloch S, Chen W, Seaman M, Chen B*, Chou JJ*. (2020). Structural Basis of Transmembrane Coupling of the HIV-1 Envelope Glycoprotein. Nature Communications, 11 (1) 1-12 PMID: 32385256

    7. Piai A#, Fu Q#, Dev J, Chou JJ*. (2017). Optimal Bicelle Size q for Solution NMR Studies of the Protein Transmembrane Partition. Chemistry, 23(6): 1361-1367 PMID: 27747952

    8. Fu Q, Zhou C, Gao H, Jiang Y, Zhou Z, Hong J, Yao W, Song A, Lin D*, Hu H*. (2009). Structural basis for ubiquitin recognition by a novel domain from human phospholipase A2-activating protein. J Biol Chem 284, 19043-19052 PMID: 19423704

    9. Xiao T#, Frey G#, Fu Q, Lavine CL, Scott DA, Seaman MS, Chou JJ, Chen B*.HIV-1 fusion inhibitors targeting the membrane-proximal external region of Env spikes. Nature Chemical Biology, 16 (5) 529-537 (2020). PMID:32152540

    10. Chen W#, Cai Y#, Fu Q, Chen B*, Guo J*, Chou JJ*. Unidirectional Presentation of Membrane Proteins in Nanoparticle-Supported Liposomes. Angew Chem Int Ed Engl, 58 (29) 9866-70. (2019). PMID:30990942

    11. Pan L#, Fu TM#, Zhao W#, Zhao L#, Chen W, Qiu C, Liu W, Liu Z, Piai A, Fu Q, Chen S*, Wu H*, Chou JJ*. Higher-Order Clustering of the Transmembrane Anchor of DR5 Drives Signaling. Cell, 176(6):1477-1489 (2019). PMID:30827683

    12. Piai A#, Dev J#, Fu Q, Chou JJ*. Stability and water accessibility of the trimeric membrane anchors of the HIV-1 envelope spikes. J Am Chem Soc, 139(51):18432-18435 (2017). PMID: 29193965

    13. Dev J#, Park D#, Fu Q, Chen J, Ha H, Ghantous F, Herrmann T, Chang W, Liu Z, Frey G, Seaman M, Chen B*, Chou JJ*. Structural basis for membrane anchoring of HIV-1 envelope spike. Science, 353(6295):172-175 (2016). PMID: 27338706

    14. Fu Q, Song A, Hu H*. Structural aspects of ubiquitin binding specificities. Curr Protein Pept Sci. 13(5): 482-489 (2012). PMID: 22812525

    15. Fu Q, Zhou C, Gao H, Jiang Y, Zhou Z, Hong J, Yao W, Song A, Lin D*, Hu H*. Structural basis for ubiquitin recognition by a novel domain from human phospholipase A2-activating protein. J Biol Chem 284, 19043-19052 (2009). PMID: 19423704

    16. Fu Q, Song A, Li S. and Hu H*. The small GTPase activity of the ROC domain from LRRK2, a Parkinson's disease related protein. Protein Pept Lett 16, 1442-1446 (2009). PMID: 20001906

    17. Fu Q, Li F. and Chen L*. Gene expression analysis of six GC-rich Gram-negative phytopathogens. Biochem Biophys Res Commun 332, 380-387 (2005). PMID: 15910748

    18. Liu S#, Fu Q#, Zhao J, Hu H*. Structural and mechanistic insights into the arginine/lysine-rich peptide motifs that interact with P97/VCP. Biochimica et Biophysica Acta (BBA)-Proteins and Proteomics 1834(12), 2672-2678 (2013). PMID: 24100225 (1equal contribution)

    19. Xie Y, Zhou C, Zhou Z, Hong J, Che M, Fu Q, Song A, Lin D*, and Hu H*. Interaction with synphilin-1 promotes inclusion formation of alpha-synuclein: mechanistic insights and pathological implication. Faseb J 24, 196-205  (2010). PMID: 19762560

    20. Song A, Zhou C, Peng Y, Gao X, Zhou Z, Fu Q, Hong J, Lin D*, Hu H*. Structural transformation of the tandem ubiquitin-interacting motifs in ataxin-3 and their cooperative interactions with ubiquitin chains. PLoS One 5(10):e13202 (2010). PMID: 20949063

    21. Wu H, Yang Y, Jiang S, Chen L, Gao H, Fu Q, Li F, Ma B and Zhang H*. DCCP and DICP: construction and analyses of databases for copper- and iron-chelating proteins. Genomics Proteomics Bioinformatics 3, 52-57  (2005). PMID: 16144523

    22. Yan X, Yang Q, Howe J, Fu Q, Wang L*. New Structural View on How Amyloid Beta Production Hints Alzheimer’s Disease Pathology. Journal of Postdoctoral Research 50, 53-56 (2014).