上述各类受体和感受器以及细胞表面蛋白是生物和外界联系的第一线,也是我们的主要研究兴趣和研究对象。目前的研究主要聚焦于(但不局限于)以下几个研究方向:
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(1)人类天然免疫受体与病原-宿主相互作用;
(2)动物感觉受体,如味觉受体,磁感应受体以及重力感受的生物学机理;
(3)植物激素受体和动物激素受体的比较研究;
(4)自然界色彩的生物物理学研究,从某种意义上来说,色彩是生物体对环境的一种结构性的适应,我们的研究主要侧重于光感应受体,色素形成的分子机理,以及自然界中的结构色彩(Structural Color)与物理学的光栅效应等,简单来说,“光,生物大分子,色彩”,三位一体。
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在探寻自然界奥秘的同时,我们也致力于发展蛋白质研究和分子生物物理学研究的新方法新思路。这即是我们探索自然界的工具,也是我们研究的根基和平台。
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北京大学生命科学学院 受体生物学实验室 隶属于生物膜与膜生物工程国家重点实验室。我们希望综合利用分子生物物理学,细胞生物学,蛋白质生物化学,结构生物学(如蛋白质晶体学,蛋白质电镜技术)和计算生物学(分子动力学和分子模拟)等方法系统阐述生物怎样感知其外界环境中的各种物理和化学因素并做出反应。
Living organisms respond to the messages they received from the world around them, and the reactions to the outside world rely on how the messages can be correctly received and coded into signals that can be processed by cells. Receptors and sensors are protein molecules that serve as transducers to receive and interpret stimuli. They are specific for the type of stimulus that they can detect. One commonly recognized categorization for receptors (or sensors) is as follows:
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(I) Chemoreceptors detect ions or other substance, including hormone receptors, immune receptors, taste receptors, et. al.
(II) Photoreceptor are light-sensitive proteins involved in the sensing and response to light in a variety of organisms, including rhodopsin, phytochrome, cryptochrome, et. al.
(III) Mechanoreceptors detect changes in pressure, or position; including receptors for touch, stretch, hearing, and equilibrium.
(IV) Thermoreceptors detect temperatures, hot or cold.
(V) Pain receptors (Nociceptors) respond to damage to body tissues leading to pain perception.
(VI) Electromagneticreceptors respond to electromagnetic waves and magnetic fields.
(VII) Gravity receptor (Gravity sensor) sense of gravity. The existance of biological gravity receptor/sensor is still mysterious.
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My lab at Peking University focuses on receptor biology, and is pursuing research in four major directions: (I) Human Innate ImmuneReceptors (with an emphasis on Host-Pathogen Interaction), (II) Animal sensory system (Sensory Receptors such as taste receptors and magnetosensors), and (III) Plant Hormone Receptors, (IV) Coloration and Structural Color (The color of an organism is a structural adaptation that helps it survive). We are also interested in developing novel eukaryotic expression systems for structural biology studies and pharmaceutical industry, which has been serving as the base and our technology platform.
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Integration of structural biology, functional biology and computational biology in our research allows us to see the future of biological interactions at the higher resolution and indynamic. Almost 15 years of research experience on receptor and sensory biology, walking through a long journey from ecology, molecular biology,biochemistry, structural biology and biophysics, now we can tackle complex receptorproteins and understand fundamental biological questions at atomic level.
代表性论文
1. Christopher S. Kollmann, Xiaopeng Bai, Ching-Hsuan Tsai, Hongfang Yang, Kenneth E. Lind, Steven R. Skinner, Zhengrong Zhu, David I. Israel, John W. Cuozzo, Barry A. Morgan, Koichi Yuki, Can Xie, Timothy A. Springer, Motomu Shimaoka, Ghotas Evindar , Application of encoded library technology (ELT) to a protein–protein interaction target: Discovery of a potent class of integrin lymphocyte function-associated antigen 1 (LFA-1) antagonists , Bioorganic & Medicinal Chemistry , 2014 , in press (online published)
2. Liu L, Jin L, Huang X, Geng Y, Li F, Qin Q, Wang R, Ji S, Zhao S, Xie Q, Wei C, Xie C, Ding B, Li Y. , OsRFPH2-10, a RING-H2 Finger E3 Ubiquitin Ligase, Is Involved in Rice Antiviral Defense in the Early Stages of Rice dwarf virus Infection , Mol Plant , 2014 , online published
3. Lin L, Tian X, Hong S, Dai P, You Q, Wang R, Feng L, Xie C, Tian ZQ, Chen X. , A bioorthogonal Raman reporter strategy for SERS detection of glycans on live cells , Angew Chem Int Ed Engl. , 2013 , 2013 Jul 8;52(28):7266-71
4. Xu X, Dong GX, Hu XS, Miao L, Zhang XL, Zhang DL, Yang HD, Zhang TY, Zou ZT, Zhang TT, Zhuang Y, Bhak J, Cho YS, Dai WT, Jiang TJ, Xie C, Li RQ, Luo SJ . , The genetic basis of white tigers , Current Biology , 2013 , 1031-1035
5. Lianshun Feng, Senlian Hong, Jie Rong, Qiancheng You, Peng Dai, Rongbing Huang, Yanhong Tan, Weiyao Hong, Can Xie, Jing Zhao, and Xing Chen , Bifunctional Unnatural Sialic Acids for Dual Metabolic Labeling of Cell-Surface Sialylated Glycans , J. Am. Chem. Soc. , 2013 , DOI: 10.1021/ja402326z. , ( co-corresponding author)
6. Xie C, Zhu J, Chen X, Mi L, Nishida N, Springer TA , Structure of an integrin with an aI domain, complement receptor type 4. , EMBO J , 2010 , 29(3): 666-679. , (It is the first complement receptor structure and also the first αI domain integrin structure.)
7. Xing Chen, Can Xie, Noritaka Nishida, Zongli Li, Thomas Walz, and Timothy A. Springer , Requirement of open headpiece conformation for activation of leukocyte integrin αXβ2 , Proc. Natl. Acad. Sci. USA , 2010 , 107: 14727-32
8. Xie C, et. al, , Stabilized Low Affinity Conformation of Integrins for Drug Discovery. , US Patent , 2008 , NP Ref: 033393-063940-P; , (The patent is about a new technology of expressing and purifying huge, heterodimeric, glycoprotein with mammalian expression systems)
9. Vorup-Jensen, T, Chi, L, Gjelstrup, LC, Jensen, UB, Jewett CA, Xie C, Shimaoka M, Linhardt RJ, Springer TA , Binding between the integrin αXβ2 (CD11c/CD18) and heparin , J. Biol. Chem. , 2007 , 282:30869-77
10. Nishida N*, Xie C*, Shimaoka M, Cheng Y, Walz T, Springer TA , Activation of leukocyte β2 integrins by conversion from bent to extended conformation , Immunity , 2006 , 583-594 (* : Co-first author) , (It is the first EM structure of aI Integrins. It also provided structural basis of antibody activation of integrin function).
11. Chen JF, Takagi J, Xie C, Xiao T, Luo BH, Springer TA , The relative influence of metal ion binding sites in the I-like domain and the interface with the hybrid domain on rolling and firm adhesion by integrin α4β7 , J. Biol. Chem. , 2004 , 279: 55556-55561
12. Xie C, Shimaoka M, Xiao T, Schwab P, Klickstein LB, Springer TA , The integrin α subunit leg extends at a Ca2+-dependent epitope in the thigh/genu interface upon activation , Proc. Natl. Acad. Sci. USA , 2004 , 101: 15422-15427
13. Xie C, Zhang JS, Zhou HL, Li J, Zhang ZG, Wang DW, Chen SY , Serine/threonine kinase activity in the putative histidine kinase-like ethylene receptor NTHK1 from tobacco , Plant J. , 2003 , 33(2):385-393 , (It is the first report of Ser/Thr kinase activity, but not Histidine kinase activity of plant ethylene receptor, which overturned a previously proposed mechanism for ethylene signaling based on histidine kinase activity of the receptors)
14. Xie C, Zhang ZG, Zhang JS, He XJ, Cao WH, He SJ, Chen SY , Spatial expression and characterization of a putative ethylene receptor protein NTHK1 in tobacco , Plant Cell Physiol. , 2002 , 43(7):810-815
15. Xie C, Zhang JS, Chen SY , Protein Phosphorylation and two-component system , Progress in Biotechnology , 2001 , 21(6), 9-14
16. Zhang JS *, Xie C *, Shen YG, Chen SY, 2001, , A two-component gene (NTHK1) encoding a putative ethylene receptor homolog is both developmently- and stress-regulated in tobacco , Thero. Appl. Genet. , 2001 , 102 (6/7): 815-824. (* : Co-first author)
17. Zhang JS, Xie C, Wu XL, Du BX, Chen SY , Tobacco two-component gene NTHK2 , Chinese Science Bulletin , 2001 , 46(7): 574-577
18. Wang WM, Zhu LH, Xie R, Xie C, Jin L , Morphological and anatomical analysis of a floral organ mutant in rice , Acta Botanica Sinica , 2000 , 42(4): 379-382
19. Xie C, Zhang JS, Chen SY , Tobacco floral homeotic gene NFBP6 is specifically expressed during pollen and ovule development , Science in China(Series C) , 1999 , 42(5),481-484
20. Zhang JS, Xie C, Li ZY, Chen SY , Expression of the plasma membrane H+-ATPase gene in response to salt stress in a rice salt-tolerance mutant and its original variety, , Theor Appl Genet. , 1999 , 99, (6), 1006-1011
21. Zhang JS, Xie C, Liu F, Liu FH, Chen SY, , 1999, , A novel tobacco gene coding for a product similar to bacterial two-component regulators , Chinese Science Bulletin , 1999 , 44(11), 1025-1029