领域：生物产业 学校：南京大学职称：教授
本结构生物学实验室隶属于南京大学生命科学学院，为医药生物技术国家重点实验室成员组。本研究组应用结构生物学手段，特别是生物大分子晶体衍射技术，综合分子生物学、细胞生物学等多学科，研究生命医学领域的重要过程。
研究方向
背景介绍
本实验室运用包括X射线晶体衍射技术和冷冻电子显微镜技术在内的结构生物学手段，辅助以生物化学，细胞生物学，计算生物学等多种技术，主要研究病毒感染机理及其引起的宿主细胞先天性免疫应答机制。本实验室致力于对病毒感染性疾病和类病毒感染的自身免疫性疾病，以及核酸代谢引起的免疫活化问题寻求分子层面的理论基础，进而为设计研发有效的治疗药物和疫苗提供支持。
病毒感染分子机制研究
病毒是世界上分布最为广泛的传染性病原体，可以感染几乎所有具有细胞结构的生命体。研究病毒蛋白的工作机理有助于了解病毒的生活史和致病机理，为开发抗病毒药物和疫苗提供支持。同时病毒也是非常有趣的研究对象，它们结构相对简单，但从基因组到蛋白质的结构和功能都呈现出了惊人的多样性。我们的研究兴趣是引发重要传染性疾病的病毒，由病毒编码的蛋白质，酶类，尤其是与宿主蛋白质发生直接相互作用的一类附件蛋白，用以回答诸如病毒如何完成侵染，复制，以及如何对抗或调节宿主免疫应答一类的问题。
Activation mechanism of ZIKV NS3pro. Overall structure of apo ZIKV NS2B-NS3pro (left ). Proteins are shown as ribbons with NS2B and NS3pro colored accordingly. The N- and C- termini of the proteins are numbered. The catalytic residues are shown as orange sticks. The inhibitor cn-716 is shown as mesh and sticks and colored in yellow. Putty representations of the superposition of apo and cn-617 complexed ZIKV NS2B-NS3pro (right). The apo structure is aligned to the complex structure. The color spectrum and the coil thickness represent the root-mean-square deviation (RMSD) of the aligned Cα atoms. The disordered regions in the apo structure are shown in magenta.
针对病毒感染的宿主天然免疫应答机制研究
研究实例
艾滋病病毒抑制因子的抗病毒分子机制研究
艾滋病病毒抑制因子是宿主天然免疫系统中的抗病毒蛋白质，这些原生蛋白质分别作用在病毒感染的特定环节，识别特定的病毒组成，干扰病毒生命周期，对病毒产生直接、迅速的强力拦截。对这些病毒抑制因子的结构功能研究可以为防治重大病毒性传染病提供新靶标和新手段，具有重要的科学意义和潜在应用价值。
Schematic illustration of the mechanism of SAMHD1 activation by allosteric nucleotide-induced tetramerization. The structure of SAMHD1 tetramer is shown in the bottom left corner. Subunits of SAMHD1 are colored differently. A total of 12 dGTP molecules are bound to the SAMHD1 tetramer, with two juxtaposed at each of the four allosteric sites (yellow) and one in each of the four substrate-binding pockets (cyan). Two inactive dimers undergo an induced allosteric conformational change at the dimer-dimer interface, thereby altering the size and shape of the substrate-binding pocket, resulting in a catalytically active enzyme.
基于结构的合理药物设计
基于靶标蛋白质三维分子结构信息，进行小分子抑制剂或激动剂的开发和检验。通过对蛋白质与小分子复合物的结构解析，为药物设计提供实验数据支持。本工作与国内外多个研究组开展合作。
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文章列表
Li T, Zhao Q, Yang X, Chen C, Yang K, Wu C, Zhang T, Duan Y, Xue X, Mi K, Ji X, Wang Z, Yang H (2018). Structural insight into the Zika virus capsid encapsulating the viral genome. Cell Research. 28, 497–499.
Buzovetsky O*, Tang C*, Knecht K, Antonucci J, Wu L, Ji X#, Xiong Y#(2018). The SAM domain of mouse SAMHD1 is critical for its activation and regulation. Nature Communication.9(1):411(#co-correspondence)
Yu Y, Jin Y, Zhou J, Ruan H, Zhao H, Lu S, Zhang Y, Li D, Ji X, Ruan BH. (2017) Ebselen: Mechanisms of Glutamate Dehydrogenase and Glutaminase Enzyme Inhibition. ACS Chemical Biology. 2017;12(12):3003-11.
ChenX*, YangK*, WuC*, ChenC, HuC, BuzovetskyO, WangZ, JiX#, XiongYand YangH#(2016). Mechanisms of activation and inhibition of Zika virus NS2B-NS3 protease. Cell Research26(11): 1260-1263.(#co-correspondence)
Antonucci J, St. Gelais C, de Silva S, YountJS, Tang C, Ji X,Shepard C,Xiong Y,Kim B,Wu L. (2016) SAMHD1-mediated HIV-1 restriction in cells does not involve ribonuclease activity. Nature Medicine22(10):1072-4
TianH*, Ji X*, Yang X*, Zhang Z, Lu Z, Yang K, Chen C, Zhao Q, Chi H, Mu Z, Xie W, Wang Z, Lou H, Yang H, Rao Z. (2016) Structural basis of Zika virus helicase in recognizingitssubstrates. Protein&Cell.2016:1-9. (*equal contribution)
Tian H*, Ji X*,Yang X*, Xie W, Yang K, Chen C, Wu C, Chi H, Mu Z, Wang Z, Yang H. (2016) The crystal structure of Zika virus helicase: basis for antiviral drug design. Protein & Cell. 2016:1-5. (*equal contribution)
Tang C, Ji X, Wu L, Xiong Y. (2015) Impaired dNTPase Activity of SAMHD1 by Phosphomimetic Mutation of T592.Journal of Biological Chemistry290(44):26352-9.
Ji X, Axford D, Owen R, Evans G, Ginn H, Sutton G, Stuart DI (2015) Polyhedra structures and the evolution of the insect viruses. Journal of Structural Biology192(1):88-99.
Ji X, Xiong Y (2015) Two Tales (Tails) of SAMHD1 Destruction by Vpx. Cell host & microbe17 (4): 425–427
Ginn HM, Messerschmidt M, Ji X, Zhang H, Axford D, Gildea RJ, Winter G, Brewster AS, Hattne J, Wagner A, Grimes JM, Evans G, Sauter NK, Sutton G, Stuart DI (2015) Structure of CPV17 polyhedrin determined by the improved analysis of serial femtosecond crystallographic data. Nature Communication6:6435
Ji X*, Tang C*, Zhao Q, Wang W, and Xiong Y (2014) Structural basis of Cellular dNTP regulation by SAMHD1.Proceedings of the National Academy of Sciences111(41):E4305-E4314 (*equal contribution)
Axford D, Ji X, Stuart DI, Sutton G (2014) In cellulo structure determination of a novel cypoviruspolyhedrin. ActaCrystallographica Section D70(5):1435-1441.
Ji X*, Wu Y*, Yan J*, Mehrens J, Yang H, DeLucia M, Hao C, Gronenborn AM, Skowronski J, Ahn J, Xiong Y (2013) Mechanism of allosteric activation of SAMHD1 by dGTP. Nature structural & molecular biology20: 1304-1309 (*equal contribution)
Yang H*, Ji X*, Zhao G, Ning J, Zhao Q, Aiken C, Gronenborn AM, Zhang P, Xiong Y (2012) Structural insight into HIV-1 capsid recognition by rhesus TRIM5α. Proceedings of the National Academy of Sciences109: 18372-18377 (*equal contribution)
Ji X, Sutton G, Evans G, Axford D, Owen R, Stuart DI (2010) Howbaculovirus polyhedra fit square pegs into round holes to robustly package viruses. EMBO Journal29(2): 505-514
