腫瘤壞死因子-α (Tumor necrosis factor-α, TNF-α) 是一種先天性免疫反應中的多效型細胞激素。而相較於哺乳類的 TNF-α 研究，硬骨魚類較缺乏，先前研究已在點帶石斑魚中發現兩種 TNF-α，並分別將其命名為 grouper TNF-α1 以及 grouper TNF-α2，兩者的胺基酸序列相似度為 35.6%，在硬骨魚類親緣關係比較中，屬兩個不同的 TNF-α 族群，且與哺乳類的差異約在 26%。而兩物種之間的 TNF-α 是否存在功能以及結構上的差異，仍需進一步的證實。在本研究中以大腸桿菌作為表現系統，且以親和性層析法純化石斑魚重組 TNF-α1 (rgTNF-α1) 及 rgTNF-α2。藉由膠體過濾層析分析發現兩者主要的分子量大小可能為三聚體。接著，在結構分析中，以 X-ray 晶體繞射實驗解析出解析度約 4.0 Å 的 rgTNFα2 晶體結構，並顯示其為單體環狀排列之三聚體構型，分別與人類及小鼠的 TNF-α 結構有高度相似性。另以小角度散射實驗確認 rgTNF-α2 在水溶液中的分子大小與形狀也呈現三聚體之構型，與晶體繞射實驗之結果相似。本研究以 rgTNF-α2 作為模板，模擬 rgTNF-α1 的蛋白質結構，並且結合跨物種之 TNF-α 的胺基酸序列比對結果發現，有些具有高度保守性的胺基酸，大多位在 Jelly-roll motif 的位置，由此可見，不同物種的 TNF-α 可能是以相同胺基酸維持它們具有的三聚體構造。

Tumor necrosis factor-α (TNF-α) is known as a pleiotropic cytokine in the innate immune system. However, few studies focused on the investigation of TNF-α in teleost. In previous study, two types of TNF-α in orange-spotted groupers (Epinephelus coioides) have been identified, named grouper TNF-α1 (gTNF-α1) and grouper TNF-α2 (gTNF-α2), respectively. Both of proteins shared 35.6% amino acid sequence identity. In the phylogenetic analysis for teleosts, they were classified into two clusters of TNF-α from teleost. Furthermore, the amino acid sequence identity among gTNF-α1, gTNF-α2 in orange-spotted grouper and TNF-α in mammalian was about 26%. However, more evidence would be needed to reveal the difference on the functional and structural differences between the TNF-α proteins of these species. In this study, recombinant grouper TNF-α1 (rgTNF-α1) and rgTNF-α2 were expressed in Escherichia coli and purified by affinity chromatography. Size exclusion chromatography analysis showed that the molecular size of rgTNF-α1 and rgTNF-α2 are closed to trimer size, repectively. The crystal structure of rgTNF-α2 was determined at 4.0 Å resolution by using the X-ray crystallography. The structure also showed that rgTNF-α2 is a ringlike trimer conformation. Additonally, small-angle X-ray scattering analysis consistantly revealed that rgTNF-α2 formed a trimer with a cylindrical shape in the aqueous solution. Comparing the structures of rgTNF-α2 with human TNF-α and mouse TNF-α respectively, the protein structures were very similar among these proteins. These results may suggest that TNF-α have a great structural homology between marine and terrestrial animals. Moreover, rgTNF-α2 was used as a template to mimic the putative protein structure of rgTNF-α1. Meanwhile, it was found some highly conserved amino acids in difference species were located in jelly-roll motif. It might mean that the trimeric structure of TNF-α in different species may maintain by the same amino acids.

林伯峰，點帶石班魚兩腫瘤壞死因子-α TNF-α1、 TNF-α2 蛋白功能性分析探討， 國立成功大學生物科技研究所碩士論文，2012。

林炫，評估不同免疫因子對於點帶石斑魚活體內誘發腫瘤壞死因子 TNF-α1 和 TNF-α2 表現量之影響 國立成功大學生物科技研究所碩士論文，2014。

蔡庚呈，利用螢光共振能量轉移技術 FRET 證明點帶石斑魚 TNF-α1 及 TNF-α2 之間的交互作用 國立成功大學生物科技研究所碩士論文，2016。

Abdalla, S. A., Horiuchi, H., Furusawa, S. and Matsuda, H. Molecular cloning and characterization of chicken tumor necrosis factor (TNF)-superfamily ligands, CD30L and TNF-related apoptosis inducing ligand (TRAIL). Journal of Veterinary Medical Science 66, 643-650, 2004.

Abola, E., Kuhn, P., Earnest, T. and Stevens, R. C. Automation of X-ray crystallography. Nature Structural and Molecular Biology 7, 973-977, 2000.

Acharya, R., Fry, E., Stuart, D., Fox, G., Rowlands, D. and Brown, F. The three-dimensional structure of foot-and-mouth disease virus at 2.9 Å resolution. Nature 337, 709-716, 1989.

Adams, P. D., Afonine, P. V., Bunkóczi, G., Chen, V. B., Echols, N., Headd, J. J., Hung, L. W., Jain, S., Kapral, G. J. and Kunstleve, R. W. G. The Phenix software for automated determination of macromolecular structures. Methods 55, 94-106, 2011.

Adams, P. D., Grosse-Kunstleve, R. W., Hung, L. W., Loerger, T. R., McCoy, A. J., Moriarty, N. W., Read, R. J., Sacchettini, J. C., Sautera, N. K. and Terwilligerf, T. C. PHENIX: building new software for automated crystallographic structure determination. Acta Crystallographica Section D: Biological Crystallography 58, 1948-1954, 2002.

Afonine, P. V., Grosse-Kunstleve, R. W., Echols, N., Headd, J. J., Moriarty, N. W., Mustyakimov, M., Terwilliger, T. C., Urzhumtsev, A., Zwart, P. H. and Adams, P. D. Towards automated crystallographic structure refinement with phenix. refine. Acta Crystallographica Section D: Biological Crystallography 68, 352-367, 2012.

Agarwal, R., Bonanno, J. B., Burley, S. K. and Swaminathan, S. Structure determination of an FMN reductase from Pseudomonas aeruginosa PA01 using sulfur anomalous signal. Acta Crystallographica Section D: Biological Crystallography 62, 383-391, 2006.

Aksentijevich, I., Galon, J. M., Soares, M., Mansfield, E., Hull, K., Oh, H. H., Goldbach-Mansky, R., Dean, J., Athreya, B. and Reginato, A. J. The tumor-necrosis-factor receptor-associated periodic syndrome: new mutations in TNFRSF1A, ancestral origins, genotype-phenotype studies, and evidence for further genetic heterogeneity of periodic fevers. The American Journal of Human Genetics 69, 301-314, 2001.

Alderson, M. R., Armitage, R. J., Tough, T. W., Strockbine, L., Fanslow, W. C. and Spriggs, M. K. CD40 expression by human monocytes: regulation by cytokines and activation of monocytes by the ligand for CD40. Journal of Experimental Medicine 178, 669-674, 1993.

An, H. J., Kim, Y. J., Song, D. H., Park, B. S., Kim, H. M., Lee, J. D., Paik, S. G., Lee, J. O. and Lee, H. Crystallographic and mutational analysis of the CD40-CD154 complex and its implications for receptor activation. Journal of Biological Chemistry 286, 11226-11235, 2011.

Baeyens, K. J., De Bondt, H. L., Raeymaekers, A., Fiers, W. and De Ranter, C. J. The structure of mouse tumour-necrosis factor at 1.4 Å resolution: towards modulation of its selectivity and trimerization. Acta Crystallographica Section D: Biological Crystallography 55, 772-778, 1999.

Baker, D. and Sali, A. Protein structure prediction and structural genomics. Science 294, 93-96, 2001.

Baneyx, F. and Mujacic, M. Recombinant protein folding and misfolding in Escherichia coli. Nature Biotechnology 22, 1399-1408, 2004.

Banner, D. W., D'Arcy, A., Janes, W., Gentz, R., Schoenfeld, H. J., Broger, C., Loetscher, H. and Lesslauer, W. Crystal structure of the soluble human 55 kd TNF receptor-human TNFβ complex: implications for TNF receptor activation. Cell 73, 431-445, 1993.

Batas, B. and Chaudhuri, J. B. Protein refolding at high concentration using size‐exclusion chromatography. Biotechnology and Bioengineering 50, 16-23, 1996.

Bernadó, P., Mylonas, E., Petoukhov, M. V., Blackledge, M. and Svergun, D. I. Structural characterization of flexible proteins using small-angle X-ray scattering. Journal of the American Chemical Society 129, 5656-5664, 2007.

Beutler, B., Greenwald, D., Hulmes, J., Chang, M., Pan, Y. C., Mathison, J., Ulevitch, R. and Cerami, A. Identity of tumour necrosis factor and the macrophage-secreted factor cachectin. Nature 316, 552-554, 1985.

Biswas, G., Kinoshita, S., Kono, T., Hikima, J. I. and Sakai, M. Evolutionary evidence of tumor necrosis factor super family members in the Japanese pufferfish (Takifugu rubripes): Comprehensive genomic identification and expression analysis. Marine Genomics 22, 25-36, 2015.

Blow, D. and Rossmann, M. The single isomorphous replacement method. Acta Crystallographica 14, 1195-1202, 1961.

Bodmer, J. L., Burns, K., Schneider, P., Hofmann, K., Steiner, V., Thome, M., Bornand, T., Hahne, M., Schröter, M. and Becker, K. TRAMP, a novel apoptosis-mediating receptor with sequence homology to tumor necrosis factor receptor 1 and Fas (Apo-1/CD95). Immunity 6, 79-88, 1997.

Bodmer, J. L., Schneider, P. and Tschopp, J. The molecular architecture of the TNF superfamily. Trends in Biochemical Sciences 27, 19-26, 2002.

Bonfadini, M. X3DPROT: a tool for distributed 3D protein structure visualization and manipulation. Journal of Applied Crystallography 24, 946-950, 1991.

Bowman, M. R., Crimmins, M., Yetz-Aldape, J., Kriz, R., Kelleher, K. and Herrmann, S. The cloning of CD70 and its identification as the ligand for CD27. The Journal of Immunology 152, 1756-1761, 1994.

Brünger, A. T. Free R value: a novel statistical quantity for assessing the accuracy of crystal structures. Nature 355, 472-475, 1992.

Brodersen, D. E., La Fortelle, E. D., Vonrhein, C., Bricogne, G., Nyborg, J. and Kjeldgaard, M. Applications of single-wavelength anomalous dispersion at high and atomic resolution. Acta Crystallographica Section D: Biological Crystallography 56, 431-441, 2000.

Brown, D., Flocco, M. M., Barril, X., Soliva, R., Davis, B., Hubbard, J., Leach, A., Hann, M., Burrows, J. N. and Griffen, E. Electron density map interpretation and atomic model of the protein. Structure-based Drug Discovery: An Overview, Royal Society of Chemistry, Cambridge, 37-38, 2007.

Brown, K., Park, S., Kanno, T., Franzoso, G. and Siebenlist, U. Mutual regulation of the transcriptional activator NF-kappa B and its inhibitor, I kappa B-alpha. Proceedings of the National Academy of Sciences of the United States of America 90, 2532-2536, 1993.

Cha, H. J., Wu, C. F., Valdes, J. J., Rao, G. and Bentley, W. E. Observations of green fluorescent protein as a fusion partner in genetically engineered Escherichia coli: monitoring protein expression and solubility. Biotechnology and Bioengineering 67, 565-574, 2000.

Chayen, N. E. A novel technique to control the rate of vapour diffusion, giving larger protein crystals. Journal of Applied Crystallography 30, 198-202, 1997.

Chen, V. B., Arendall, W. B., Headd, J. J., Keedy, D. A., Immormino, R. M., Kapral, G. J., Murray, L. W., Richardson, J. S. and Richardson, D. C. MolProbity: all-atom structure validation for macromolecular crystallography. Acta Crystallographica Section D: Biological Crystallography 66, 12-21, 2010.

Chicheportiche, Y., Bourdon, P. R., Xu, H., Hsu, Y. M., Scott, H., Hession, C., Garcia, I. and Browning, J. L. TWEAK, a new secreted ligand in the tumor necrosis factor family that weakly induces apoptosis. Journal of Biological Chemistry 272, 32401-32410, 1997.

Chu, C. S., Lee, K. T., Cheng, K. H., Lee, M. Y., Kuo, H. F., Lin, T. H., Su, H. M., Voon, W. C., Sheu, S. H. and Lai, W. T. Postchallenge responses of nitrotyrosine and TNF-alpha during 75-g oral glucose tolerance test are associated with the presence of coronary artery diseases in patients with prediabetes. Cardiovascular Diabetology 11, 21-31, 2012.

Darnay, B. G., Haridas, V., Ni, J., Moore, P. A. and Aggarwal, B. B. Characterization of the intracellular domain of receptor activator of NF-κB (RANK) Interaction with tumor necrosis factor receptor-associated factors and activation of NF-κB and c-Jun N-terminal kinase. Journal of Biological Chemistry 273, 20551-20555, 1998.

Darnay, B. G., Ni, J., Moore, P. A. and Aggarwal, B. B. Activation of NF-κB by RANK requires tumor necrosis factor receptor-associated factor (TRAF) 6 and NF-κB-inducing kinase identification of a novel TRAF6 interaction motif. Journal of Biological Chemistry 274, 7724-7731, 1999.

Dessau, M. A. and Modis, Y. Protein crystallization for X-ray crystallography. Journal of Visualized Experiments 47, 2285-2296, 2011.

Di-Poï, N. and Milinkovitch, M. The anatomical placode in reptile scale morphogenesis indicates shared ancestry among skin appendages in amniotes. Science Advances 2, e1600708, 2016.

Dickerson, R., Kendrew, J. T. and Strandberg, B. The crystal structure of myoglobin: phase determination to a resolution of 2 Å by the method of isomorphous replacement. Acta Crystallographica 14, 1188-1195, 1961.

Eck, M. J. and Sprang, S. R. The structure of tumor necrosis factor-alpha at 2.6 Å resolution. Implications for receptor binding. Journal of Biological Chemistry 264, 17595-17605, 1989.

Emsley, P. and Cowtan, K. Coot: model-building tools for molecular graphics. Acta Crystallographica Section D: Biological Crystallography 60, 2126-2132, 2004.

Fontaine, V., Mohand-Said, S., Hanoteau, N., Pfizenmaier, K. and Eisel, U. Neurodegenerative and neuroprotective effects of tumor necrosis factor (TNF) in retinal ischemia: opposite roles of TNF receptor 1 and TNF receptor 2. Journal Neuroscience 22, 1-7, 2002.

Förster, F., Webb, B., Krukenberg, K. A., Tsuruta, H., Agard, D. A. and Sali, A. Integration of small-angle X-ray scattering data into structural modeling of proteins and their assemblies. Journal of Molecular Biology 382, 1089-1106, 2008.

Fortier, S., Moore, N. J. and Fraser, M. E. A direct-methods solution to the phase problem in the single isomorphous replacement case: theoretical basis and initial applications. Acta Crystallographica Section A: Foundations of Crystallography 41, 571-577, 1985.

Franke, D. and Svergun, D. I. DAMMIF, a program for rapid ab-initio shape determination in small-angle scattering. Journal of Applied Crystallography 42, 342-346, 2009.

Fu, Q., Fu, T. M., Cruz, A. C., Sengupta, P., Thomas, S. K., Wang, S., Siegel, R. M., Wu, H. and Chou, J. J. Structural basis and functional role of intramembrane trimerization of the Fas/CD95 death receptor. Molecular Cell 61, 602-613, 2016.

Giorgetti, A., Raimondo, D., Miele, A. E. and Tramontano, A. Evaluating the usefulness of protein structure models for molecular replacement. Bioinformatics 21, ii72-ii76, 2005.

Gopal, G. J. and Kumar, A. Strategies for the production of recombinant protein in Escherichia coli. The Protein Journal 32, 419-425, 2013.

Gopal, K., Romo, T. D., Sacchettini, J. C. and Ioerger, T. R. Determining relevant features to recognize electron density patterns in X-ray protein crystallography. Journal of Bioinformatics and Computational Biology 3, 645-676, 2005.

Granger, G. A., Orr, S. and Yamamoto, R. Lymphotoxins, macrophage cytotoxins, and tumor necrosis factors: an interrelated family of antitumor effector molecules. Journal of Clinical Immunology 5, 217-219, 1985.

Grayfer, L., Walsh, J. G. and Belosevic, M. Characterization and functional analysis of goldfish (Carassius auratus L.) tumor necrosis factor-alpha. Developmental and Comparative Immunology 32, 532-543, 2008.

Grell, M., Douni, E., Wajant, H., Löhden, M., Clauss, M., Maxeiner, B., Georgopoulos, S., Lesslauer, W., Kollias, G. and Pfizenmaier, K. The transmembrane form of tumor necrosis factor is the prime activating ligand of the 80 kDa tumor necrosis factor receptor. Cell 83, 793-802, 1995.

Gurney, A., Marsters, S., Huang, A., Pitti, R., Mark, M., Baldwin, D., Gray, A., Dowd, P., Brush, J. and Heldens, S. Identification of a new member of the tumor necrosis factor family and its receptor, a human ortholog of mouse GITR. Current Biology 9, 215-218, 1999.

Hammond, J. B. and Kruger, N. J. The bradford method for protein quantitation. Methods in Molecular Biology, Humana Press, New York, 25-32, 1988.

Hannig, G. and Makrides, S. C. Strategies for optimizing heterologous protein expression in Escherichia coli. Trends in Biotechnology 16, 54-60, 1998.

Hartmann, W. K., Saptharishi, N., Yang, X. Y., Mitra, G. and Soman, G. Characterization and analysis of thermal denaturation of antibodies by size exclusion high-performance liquid chromatography with quadruple detection. Analytical Biochemistry 325, 227-239, 2004.

Helliwell, J. and Helliwell, M. X-Ray crystallography in structural chemistry and molecular biology. Chemical Communications 14, 1595-1602, 1996.

Hendrickson, W. A., Smith, J. L., Phizackerley, R. P. and Merritt, E. A. Crystallographic structure analysis of lamprey hemoglobin from anomalous dispersion of synchrotron radiation. Proteins: Structure, Function, and Bioinformatics 4, 77-88, 1988.

Hendrickson, W. A. and Teeter, M. M. Structure of the hydrophobic protein crambin determined directly from the anomalous scattering of sulphur. Nature 290, 107-113, 1981.

Hoffmann, F. and Rinas, U. Kinetics of heat‐shock response and inclusion body formation during temperature‐induced production of basic fibroblast growth factor in high‐cell‐density cultures of recombinant Escherichia coli. Biotechnology Progress 16, 1000-1007, 2000.

Holm, L. and Sander, C. Protein structure comparison by alignment of distance matrices. Journal of Molecular Biology 233, 123-138, 1993.

Hong, S., Li, R., Xu, Q., Secombes, C. J. and Wang, T. Two types of TNF-α exist in teleost fish: phylogeny, expression, and bioactivity analysis of type-II TNF-α3 in rainbow trout Oncorhynchus mykiss. The Journal of Immunology 191, 5959-5972, 2013.

Houborg, K., Harris, P., Petersen, J., Rowland, P., Poulsen, J. C., Schneider, P., Vind, J. and Larsen, S. Impact of the physical and chemical environment on the molecular structure of Coprinus cinereus peroxidase. Acta Crystallographica Section D: Biological Crystallography 59, 989-996, 2003.

Hsu, H., Shu, H. B., Pan, M. G. and Goeddel, D. V. TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways. Cell 84, 299-308, 1996.

Hsu, H., Xiong, J. and Goeddel, D. V. The TNF receptor 1-associated protein TRADD signals cell death and NF-κB activation. Cell 81, 495-504, 1995.

Idriss, H. T. and Naismith, J. H. TNFα and the TNF receptor superfamily: structure‐function relationship (s). Microscopy Research and Technique 50, 184-195, 2000.

Ioannou, Y. A., Zeidner, K. M., Grace, M. E. and Desnick, R. J. Human α-galactosidase A: glycosylation site 3 is essential for enzyme solubility. Biochemical Journal 332, 789-797, 1998.

Jin, T., Guo, F., Kim, S., Howard, A. and Zhang, Y. Z. X-ray crystal structure of TNF ligand family member TL1A at 2.1 Å. Biochemical and Biophysical Research Communications 364, 1-6, 2007.

Jones, E., Stuart, D. and Walker, N. Structure of tumour necrosis factor. Nature 338, 225-258, 1989.

Kane, J. F. and Hartley, D. L. Formation of recombinant protein inclusion bodies in Escherichia coli. Trends in Biotechnology 6, 95-101, 1988.

Karin, M., Liu, Z. G. and Zandi, E. AP-1 function and regulation. Current Opinion in Cell Biology 9, 240-246, 1997.

Kehrl, J. H., Miller, A. and Fauci, A. S. Effect of tumor necrosis factor alpha on mitogen-activated human B cells. Journal of Experimental Medicine 166, 786-791, 1987.

Kim, E. Y., Priatel, J. J., Teh, S. J. and Teh, H. S. TNF receptor type 2 (p75) functions as a costimulator for antigen-driven T cell responses in vivo. The Journal of Immunology 176, 1026-1035, 2006.

Kim, E. Y. and Teh, H. S. TNF type 2 receptor (p75) lowers the threshold of T cell activation. The Journal of Immunology 167, 6812-6820, 2001.

Konarev, P. V., Petoukhov, M. V., Volkov, V. V. and Svergun, D. I. ATSAS 2.1, a program package for small-angle scattering data analysis. Journal of Applied Crystallography 39, 277-286, 2006.

Kuga, S. Pore size distribution analysis of gel substances by size exclusion chromatography. Journal of Chromatography A 206, 449-461, 1981.

Lam, F. W., Wu, S. Y., Lin, S. J., Lin, C. C., Chen, Y. M., Wang, H. C., Chen, T. Y., Lin, H. T. and Lin, J. H. The expression of two novel orange-spotted grouper (Epinephelus coioides) TNF genes in peripheral blood leukocytes, various organs, and fish larvae. Fish and Shellfish Immunology 30, 618-629, 2011.

Lam, J., Nelson, C. A., Ross, F. P., Teitelbaum, S. L. and Fremont, D. H. Crystal structure of the TRANCE/RANKL cytokine reveals determinants of receptor-ligand specificity. The Journal of Clinical Investigation 108, 971-979, 2001.

Lantz, M., Gullberg, U., Nilsson, E. and Olsson, I. Characterization in vitro of a human tumor necrosis factor-binding protein. A soluble form of a tumor necrosis factor receptor. The Journal of Clinical Investigation 86, 1396-1402, 1990.

Lavallie, E. R., DiBlasio, E. A., Kovacic, S., Grant, K. L., Schendel, P. F. and McCoy, J. M. A thioredoxin gene fusion expression system that circumvents inclusion body formation in the E. coli cytoplasm. Bio/Technology 11, 187-193, 1993.

Leist, M., Gantner, F., Jilg, S. and Wendel, A. Activation of the 55 kDa TNF receptor is necessary and sufficient for TNF-induced liver failure, hepatocyte apoptosis, and nitrite release. The Journal of Immunology 154, 1307-1316, 1995.

Lewit, A., Roger, B., Richard, F., Thierry, K., Patrice, P., Tavernier, V. J., Hauquier, G. and Fiers, W. Structure of tumour necrosis factor by X-ray solution scattering and preliminary studies by single crystal X-ray diffraction. Journal of Molecular Biology 199, 389-392, 1988.

Liu, C., Walter, T. S., Huang, P., Zhang, S., Zhu, X., Wu, Y., Wedderburn, L. R., Tang, P., Owens, R. J. and Stuart, D. I. Structural and functional insights of RANKL-RANK interaction and signaling. The Journal of Immunology 184, 6910-6919, 2010.

Loetscher, H., Gentz, R., Zulauf, M., Lustig, A., Tabuchi, H., Schlaeger, E., Brockhaus, M., Gallati, H., Manneberg, M. and Lesslauer, W. Recombinant 55-kDa tumor necrosis factor (TNF) receptor. Stoichiometry of binding to TNF alpha and TNF beta and inhibition of TNF activity. Journal of Biological Chemistry 266, 18324-18329, 1991.
Lovell, S. C., Davis, I. W., Arendall III, W. B., De Bakker, P. I., Word, J. M., Prisant, M. G., Richardson, J. S. and Richardson, D. C. Structure validation by Cα geometry: ϕ, ψ and Cβ deviation. Proteins: Structure, Function, and Bioinformatics 50, 437-450, 2003.

Luan, X., Lu, Q., Jiang, Y., Zhang, S., Wang, Q., Yuan, H., Zhao, W., Wang, J. and Wang, X. Crystal structure of human RANKL complexed with its decoy receptor osteoprotegerin. The Journal of Immunology 189, 245-252, 2012.

Lubkowski, J., Sonmez, C., Smirnov, S. V., Anishkin, A., Kotenko, S. V. and Wlodawer, A. Crystal structure of the labile complex of IL-24 with the extracellular domains of IL-22R1 and IL-20R2. The Journal of Immunology 201, 2082-2093, 2018.

Ma, T. Y., Wu, J. Y., Gao, X. K., Wang, J. Y., Zhan, X. L. and Li, W. S. Molecular cloning, functional identification and expressional analyses of FasL in Tilapia, Oreochromis niloticus. Developmental and Comparative Immunology 46, 448-460, 2014.

Marsters, S. A., Frutkin, A. D., Simpson, N. J., Fendly, B. M. and Ashkenazi, A. Identification of cysteine-rich domains of the type 1 tumor necrosis factor receptor involved in ligand binding. Journal of Biological Chemistry 267, 5747-5750, 1992.

Mawaribuchi, S., Tamura, K., Okano, S., Takayama, S., Yaoita, Y., Shiba, T., Takamatsu, N. and Ito, M. Tumor necrosis factor-α attenuates thyroid hormone-induced apoptosis in vascular endothelial cell line XLgoo established from Xenopus tadpole tails. Endocrinology 149, 3379-3389, 2008.

McPherson, A. Introduction to protein crystallization. Methods 34, 254-265, 2004.

Mertens, H. D. and Svergun, D. I. Structural characterization of proteins and complexes using small-angle X-ray solution scattering. Journal of Structural Biology 172, 128-141, 2010.

Miettinen, M., Vuopio-Varkila, J. and Varkila, K. Production of human tumor necrosis factor alpha, interleukin-6, and interleukin-10 is induced by lactic acid bacteria. Infection and Immunity 64, 5403-5405, 1996.

Moore, P. A., Belvedere, O., Orr, A., Pieri, K., La Fleur, D. W., Feng, P., Soppet, D., Charters, M., Gentz, R. and Parmelee, D. BLyS: member of the tumor necrosis factor family and B lymphocyte stimulator. Science 285, 260-263, 1999.

Mukai, Y., Nakamura, T., Yoshikawa, M., Yoshioka, Y., Tsunoda, S. I., Nakagawa, S., Yamagata, Y. and Tsutsumi, Y. Solution of the structure of the TNF-TNFR2 complex. Science Signal 3, ra83, 2010.

Murthy, H. M. K. Use of multiple-wavelength anomalous diffraction measurements in ab initio phase determination for macromolecular structures. Crystallographic Methods and Protocols, Human Press, New York, 127-151, 1996.

Nagata, S. Fas and Fas ligand: a death factor and its receptor. Advances in Immunology 57, 129-144, 1994.

Naismith, J. H., Devine, T. Q., Brandhuber, B. J. and Sprang, S. R. Crystallographic evidence for dimerization of unliganded tumor necrosis factor receptor. Journal of Biological Chemistry 270, 13303-13307, 1995.

Nandhagopal, N., Simpson, A. A., Gurnon, J. R., Yan, X., Baker, T. S., Graves, M. V., Van Etten, J. L. and Rossmann, M. G. The structure and evolution of the major capsid protein of a large, lipid-containing DNA virus. Proceedings of the National Academy of Sciences of the United States of America 99, 14758-14763, 2002.

Nascimento, D. S., Pereira, P. J., Reis, M. I., Do Vale, A., Zou, J., Silva, M. T., Secombes, C. J. and Dos Santos, N. M. Molecular cloning and expression analysis of sea bass (Dicentrarchus labrax L.) tumor necrosis factor-α (TNF-α). Fish and Shellfish Immunology 23, 701-710, 2007.

Ni, C. Z., Welsh, K., Leo, E., Chiou, C. K., Wu, H., Reed, J. C. and Ely, K. R. Molecular basis for CD40 signaling mediated by TRAF3. Proceedings of the National Academy of Sciences of the United States of America 97, 10395-10399, 2000.

Nienaber, V. L., Richardson, P. L., Klighofer, V., Bouska, J. J., Giranda, V. L. and Greer, J. Discovering novel ligands for macromolecules using X-ray crystallographic screening. Nature Biotechnology 18, 1105-1108, 2000.

Nocentini, G., Giunchi, L., Ronchetti, S., Krausz, L. T., Bartoli, A., Moraca, R., Migliorati, G. and Riccardi, C. A new member of the tumor necrosis factor/nerve growth factor receptor family inhibits T cell receptor-induced apoptosis. Proceedings of the National Academy of Sciences of the United States of America 94, 6216-6221, 1997.

Oeser, T., Wei, R., Baumgarten, T., Billig, S., Föllner, C. and Zimmermann, W. High level expression of a hydrophobic poly (ethylene terephthalate)-hydrolyzing carboxylesterase from Thermobifida fusca KW3 in Escherichia coli BL21(DE3). Journal of Biotechnology 146, 100-104, 2010.

Otwinowski, Z. and Minor, W. Processing of X-ray diffraction data collected in oscillation mode. Methods Enzymology 276, 307-326, 1997.

Palladino, M., Shalaby, M. R., Kramer, S., Ferraiolo, B., Baughman, R., Deleo, A., Crase, D., Marafino, B., Aggarwal, B. and Figari, I. Characterization of the antitumor activities of human tumor necrosis factor-alpha and the comparison with other cytokines: induction of tumor-specific immunity. The Journal of Immunology 138, 4023-4032, 1987.

Park, A. and Baichwal, V. R. Systematic mutational analysis of the death domain of the tumor necrosis factor receptor 1-associated protein TRADD. Journal of Biological Chemistry 271, 9858-9862, 1996.

Pearson, W. R. An introduction to sequence similarity (“homology”) searching. Current Protocols in Bioinformatics 42, 3.1.1-3.1.8, 2013.

Pennica, D., Nedwin, G. E., Hayflick, J. S., Seeburg, P. H., Derynck, R., Palladino, M. A., Kohr, W. J., Aggarwal, B. B. and Goeddel, D. V. Human tumour necrosis factor: precursor structure, expression and homology to lymphotoxin. Nature 312, 724-729, 1984.

Perron-Savard, P., De Crescenzo, G. and Le Moual, H. Dimerization and DNA binding of the Salmonella enterica PhoP response regulator are phosphorylation independent. Microbiology 151, 3979-3987, 2005.

Pierri, C. L., De Grassi, A. and Turi, A. Lattices for ab initio protein structure prediction. Proteins: Structure, Function, and Bioinformatics 73, 351-361, 2008.

Qian, B., Raman, S., Das, R., Bradley, P., McCoy, A. J., Read, R. J. and Baker, D. High-resolution structure prediction and the crystallographic phase problem. Nature 450, 259-264, 2007.

Ramachandran, S., Kota, P., Ding, F. and Dokholyan, N. V. Automated minimization of steric clashes in protein structures. Proteins: Structure, Function, and Bioinformatics 79, 261-270, 2011.

Ramakrishnan, V. and Biou, V. Treatment of multiwavelength anomalous diffraction data as a special case of multiple isomorphous replacement. Methods in Enzymology 276, 538-557. 1997.

Rambo, R. P. and Tainer, J. A. Accurate assessment of mass, models and resolution by small-angle scattering. Nature 496, 477-481, 2013.

Reinhard, C., Shamoon, B., Shyamala, V. and Williams, L. T. Tumor necrosis factor α‐induced activation of c‐jun N‐terminal kinase is mediated by TRAF2. The European Molecular Biology Organization Journal 16, 1080-1092, 1997.

Reva, B. A., Finkelstein, A. V. and Skolnick, J. What is the probability of a chance prediction of a protein structure with an rmsd of 6 Å? Folding and Design 3, 141-147, 1998.

Reynolds, R., Remington, S., Weaver, L., Fisher, R., Anderson, W., Ammon, H. and Matthews, B. Structure of a serine protease from rat mast cells determined from twinned crystals by isomorphous and molecular replacement. Acta Crystallographica Section B: Structural Science 41, 139-147, 1985.
Roberts, N. J., Zhou, S., Diaz Jr, L. A. and Holdhoff, M. Systemic use of tumor necrosis factor alpha as an anticancer agent. Oncotarget 2, 739-751, 2011.

Rohde, F., Schusser, B., Hron, T., Farkašová, H., Plachý, J., Härtle, S., Hejnar, J., Elleder, D. and Kaspers, B. Characterization of chicken tumor necrosis factor-α, a long missed cytokine in birds. Frontiers in Immunology 9, 605, 2018.

Rossmann, M. G. The molecular replacement method. Acta Crystallographica Section A 46, 73-82, 1990.

Rothe, M., Sarma, V., Dixit, V. M. and Goeddel, D. V. TRAF2-mediated activation of NF-kappa B by TNF receptor 2 and CD40. Science 269, 1424-1427, 1995.

Sadhukhan, R. and Sen, I. Different glycosylation requirements for the synthesis of enzymatically active angiotensin-converting enzyme in mammalian cells and yeast. Journal of Biological Chemistry 271, 6429-6434, 1996.

Saeij, J. P., Stet, R. J., De Vries, B. J., Van Muiswinkel, W. B. and Wiegertjes, G. F. Molecular and functional characterization of carp TNF: a link between TNF polymorphism and trypanotolerance? Developmental and Comparative Immunology 27, 29-41, 2003.

Saperstein, S., Huyck, H., Kimball, E., Johnston, C., Finkelstein, J. and Pryhuber, G. The effects of interleukin-1β in tumor necrosis factor-α-induced acute pulmonary inflammation in mice. Mediators of Inflammation 2009, 958658, 2009.

Savan, R., Aman, A., Nakao, M., Watanuki, H. and Sakai, M. Discovery of a novel immunoglobulin heavy chain gene chimera from common carp (Cyprinus carpio L.). Immunogenetics 57, 458-463, 2005.

Scherer, S. and Göbel, T. W. Characterisation of chicken OX40 and OX40L. Developmental and Comparative Immunology 82, 128-138, 2018.

Schneider, P., MacKay, F., Steiner, V., Hofmann, K., Bodmer, J. L., Holler, N., Ambrose, C., Lawton, P., Bixler, S. and Acha-Orbea, H. BAFF, a novel ligand of the tumor necrosis factor family, stimulates B cell growth. Journal of Experimental Medicine 189, 1747-1756, 1999.

Schneider, P., Street, S. L., Gaide, O., Hertig, S., Tardivel, A., Tschopp, J., Runkel, L., Alevizopoulos, K., Ferguson, B. M. and Zonana, J. Mutations leading to X-linked hypohidrotic ectodermal dysplasia affect three major functional domains in the tumor necrosis factor family member ectodysplasin-A. Journal of Biological Chemistry 276, 18819-18827, 2001.

Shapiro, L. and Scherer, P. E. The crystal structure of a complement-1q family protein suggests an evolutionary link to tumor necrosis factor. Current Biology 8, 335-340, 1998.

Sheikh, N. and Jones, L. CD54 is a surrogate marker of antigen presenting cell activation. Cancer Immunology, Immunotherapy 57, 1381-1390, 2008.

Sheridan, J. P., Marsters, S. A., Pitti, R. M., Gurney, A., Skubatch, M., Baldwin, D., Ramakrishnan, L., Gray, C. L., Baker, K. and Wood, W. I. Control of TRAIL-induced apoptosis by a family of signaling and decoy receptors. Science 277, 818-821, 1997.

Sørensen, H. P., Sperling-Petersen, H. U. and Mortensen, K. K. Dialysis strategies for protein refolding: preparative streptavidin production. Protein Expression and Purification 31, 149-154, 2003.

Strange, R. W., Antonyuk, S. V., Hough, M. A., Doucette, P. A., Valentine, J. S. and Hasnain, S. S. Variable metallation of human superoxide dismutase: atomic resolution crystal structures of Cu-Zn, Zn-Zn and as-isolated wild-type enzymes. Journal of Molecular Biology 356, 1152-1162, 2006.

Suda, T., Takahashi, T., Golstein, P. and Nagata, S. Molecular cloning and expression of the Fas ligand, a novel member of the tumor necrosis factor family. Cell 75, 1169-1178, 1993.

Svergun, D. I, Barberato, C. and Koch, M. H. CRYSOL-a program to evaluate X-ray solution scattering of biological macromolecules from atomic coordinates. Journal of Applied Crystallography 28, 768-773, 1995.

Svergun, D. I. and Koch, M. H. Advances in structure analysis using small-angle scattering in solution. Current Opinion in Structural Biology 12, 654-660, 2002.

Svergun, D. I. and Koch, M. H. Small-angle scattering studies of biological macromolecules in solution. Reports on Progress in Physics 66, 1735-1782, 2003.

Svergun, D. I., Petoukhov, M. V. and Koch, M. H. Determination of domain structure of proteins from X-ray solution scattering. Biophysical Journal 80, 2946-2953, 2001.

Tafalla, C. and Granja, A. G. Novel insights on the regulation of B cell functionality by members of the TNF superfamily in jawed fish. Frontiers in Immunology 9, 1285, 2018.

Takakura‐Yamamoto, R., Yamamoto, S., Fukuda, S. and Kurimoto, M. O‐glycosylated species of natural human tumor‐necrosis factor‐α. European Journal of Biochemistry 235, 431-437, 1996.

Tamura, K., Mawaribuchi, S., Yoshimoto, S., Shiba, T., Takamatsu, N. and Ito, M. Tumor necrosis factor-related apoptosis-inducing ligand 1 (TRAIL1) enhances the transition of red blood cells from the larval to adult type during metamorphosis in Xenopus. Blood 115, 850-859, 2010.

Tang, P., Hung, M. C. and Klostergaard, J. Human pro-tumor necrosis factor is a homotrimer. Biochemistry 35, 8216-8225, 1996.

Tartaglia, L., Goeddel, D., Reynolds, C., Figari, I., Weber, R., Fendly, B. and Palladino, M. Stimulation of human T-cell proliferation by specific activation of the 75-kDa tumor necrosis factor receptor. The Journal of Immunology 151, 4637-4641, 1993.

Tayyab, S., Qamar, S. and Islam, M. Size exclusion chromatography and size exclusion HPLC of proteins. Biochemical Education 19, 149-152, 1991.
Terwilliger, T. and Berendzen, J. Correlated phasing of multiple isomorphous replacement data. Acta Crystallographica Section D 52, 749-757, 1996.

Tracey, K., Wei, H., Manogue, K. R., Fong, Y., Hesse, D. G., Nguyen, H. T., Kuo, G. C., Beutler, B., Cotran, R. and Cerami, A. Cachectin/tumor necrosis factor induces cachexia, anemia, and inflammation. Journal of Experimental Medicine 167, 1211-1227, 1988.

Trewhella, J., Carlson, V. A., Curtis, E. H. and Heidorn, D. B. Differences in the solution structures of oxidized and reduced cytochrome c measured by small-angle X-ray scattering. Biochemistry 27, 1121-1125, 1988.

Tufa, D. M., Chatterjee, D., Low, H. Z., Schmidt, R. E. and Jacobs, R. TNFR2 and IL‐12 coactivation enables slanDCs to support NK‐cell function via membrane‐bound TNF‐α. European Journal of Immunology 44, 3717-3728, 2014.

Urzhumtsev, A. How to calculate planarity restraints. Acta Crystallographica Section A: Foundations of Crystallography 47, 723-727, 1991.

Van der Sloot, A. M., Tur, V., Szegezdi, E., Mullally, M. M., Cool, R. H., Samali, A., Serrano, L. and Quax, W. J. Designed tumor necrosis factor-related apoptosis-inducing ligand variants initiating apoptosis exclusively via the DR5 receptor. Proceedings of the National Academy of Sciences of the United States of America 103, 8634-8639, 2006.

Waage, A., Halstensen, A., Shalaby, R., Brandtzaeg, P., Kierulf, P. and Espevik, T. Local production of tumor necrosis factor alpha, interleukin 1, and interleukin 6 in meningococcal meningitis. Relation to the inflammatory response. Journal of Experimental Medicine 170, 1859-1867, 1989.

Walter, R. L., Ealick, S. E., Friedman, A. M., Blake II, R. C., Proctor, P. and Shoham, M. Multiple wavelength anomalous diffraction (MAD) crystal structure of rusticyanin: a highly oxidizing cupredoxin with extreme acid stability. Journal of Molecular Biology 263, 730-751, 1996.

Walton, T. A. and Sousa, M. C. Crystal structure of Skp, a prefoldin-like chaperone that protects soluble and membrane proteins from aggregation. Molecular Cell 15, 367-374, 2004.

Welinder, K. G. and Tams, J. Effects of glycosylation on protein folding, stability and solubility. Studies of chemically modified or engineered plant and fungal peroxidases. Progress in Biotechnology 10, 205-210. 1995.

Wiencek, J. M. New strategies for protein crystal growth. Annual Review of Biomedical Engineering 1, 505-534, 1999.

Wittwer, D., Franchini, A., Ottaviani, E. and Wiesner, A. Presence of IL-1- and TNF-like molecules in Galleria Mellonella(Lepidoptera) haemocytes and in an insect cell line from Estigmene Acraea(Lepidoptera). Cytokine 11, 637-642, 1999.

Yang, L., Zhou, L., Zong, X., Cao, X., Ji, X., Gu, W. and Zhang, S. Characterization of the molecular structure, expression and bioactivity of the TNFSF13B (BAFF) gene of the south african clawed frog, Xenopus laevis. International Immunopharmacology 15, 478-487, 2013.

Ye, H., Park, Y. C., Kreishman, M., Kieff, E. and Wu, H. The structural basis for the recognition of diverse receptor sequences by TRAF2. Molecular Cell 4, 321-330, 1999.

Zhai, Y., Ni, J., Jiang, G. W., Lu, J., Xing, L., Lincoln, C., Carter, K. C., Janat, F., Kozak, D. and Xu, S. VEGI, a novel cytokine of the tumor necrosis factor family, is an angiogenesis inhibitor that suppresses the growth of colon carcinomas in vivo. The Federation of European Biochemical Societies Journal 13, 181-189, 1999.

Zhang, A., Chen, D., Wei, H., Du, L., Zhao, T., Wang, X. and Zhou, H. Functional characterization of TNF-α in grass carp head kidney leukocytes: induction and involvement in the regulation of NF-κB signaling. Fish and Shellfish Immunology 33, 1123-1132, 2012.

Zhang, J. X., Song, R., Sang, M., Sun, S. Q., Ma, L., Zhang, J. and Zhang, S. Q. Molecular and functional characterization of BAFF from the yangtze alligator (Alligator sinensis, Alligatoridae). Zoology 118, 325-333, 2015.

Zou, J., Secombes, C. J., Long, S., Miller, N., Clem, L. and Chinchar, V. Molecular identification and expression analysis of tumor necrosis factor in channel catfish (Ictalurus punctatus). Developmental and Comparative Immunology 27, 845-858, 2003.

Zou, J., Wang, T., Hirono, I., Aoki, T., Inagawa, H., Honda, T., Soma, G. I., Ototake, M., Nakanishi, T. and Ellis, A. Differential expression of two tumor necrosis factor genes in rainbow trout, Oncorhynchus mykiss. Developmental and Comparative Immunology 26, 161-172, 2002.