1tnf Citations

The structure of tumor necrosis factor-alpha at 2.6 A resolution. Implications for receptor binding.

J. Biol. Chem. 264 17595-605 (1989)
Cited: 272 times
EuropePMC logo PMID: 2551905

Abstract

The three-dimensional structure of tumor necrosis factor (TNF-alpha), a protein hormone secreted by macrophages, has been determined at 2.6 A resolution by x-ray crystallography. Phases were determined by multiple isomorphous replacement using data collected from five heavy atom derivatives. The multiple isomorphous replacement phases were further improved by real space symmetry averaging, exploiting the noncrystallographic 3-fold symmetry of the TNF-alpha trimer. An atomic model corresponding to the known amino acid sequence of TNF-alpha was readily built into the electron density map calculated with these improved phases. The 17,350-dalton monomer forms an elongated, antiparallel beta-pleated sheet sandwich with a "jelly-roll" topology. Three monomers associate intimately about a 3-fold axis of symmetry to form a compact bell-shaped trimer. Examination of the model and comparison to known protein structures reveals striking structural homology to several viral coat proteins, particularly satellite tobacco necrosis virus. Locations of residues conserved between TNF-alpha and lymphotoxin (TNF-beta, a related cytokine known to bind to the same receptors as TNF-alpha) suggest that lymphotoxin, like TNF-alpha, binds to the receptor as a trimer and that the general site of interaction with the receptor is at the "base" of the trimer.

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  1. HIV-1, methamphetamine and astrocytes at neuroinflammatory Crossroads. Borgmann K, Ghorpade A. Front Microbiol 6 1143 (2015)
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Articles - 1tnf mentioned but not cited (16)

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Reviews citing this publication (114)

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  5. The molecular architecture of the TNF superfamily. Bodmer JL, Schneider P, Tschopp J. Trends Biochem. Sci. 27 19-26 (2002)
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  22. Death to the bad guys: targeting cancer via Apo2L/TRAIL. Bouralexis S, Findlay DM, Evdokiou A. Apoptosis 10 35-51 (2005)
  23. A family of ligands for the TNF receptor superfamily. Cosman D. Stem Cells 12 440-455 (1994)
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  60. Principles of antibody-mediated TNF receptor activation. Wajant H. Cell Death Differ. 22 1727-1741 (2015)
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  62. The role of inflammation in the initiation of osteoarthritis after meniscal damage. Edd SN, Giori NJ, Andriacchi TP. J Biomech 48 1420-1426 (2015)
  63. TNF superfamily protein-protein interactions: feasibility of small- molecule modulation. Song Y, Buchwald P. Curr Drug Targets 16 393-408 (2015)
  64. Death receptor agonist therapies for cancer, which is the right TRAIL? Holland PM. Cytokine Growth Factor Rev. 25 185-193 (2014)
  65. Regulation and dysregulation of tumor necrosis factor receptor-1. Puimège L, Libert C, Van Hauwermeiren F. Cytokine Growth Factor Rev. 25 285-300 (2014)
  66. Functional and structural features of adipokine family. Raucci R, Rusolo F, Sharma A, Colonna G, Castello G, Costantini S. Cytokine 61 1-14 (2013)
  67. TNFα in myocardial ischemia/reperfusion, remodeling and heart failure. Kleinbongard P, Schulz R, Heusch G. Heart Fail Rev 16 49-69 (2011)
  68. TNF and ubiquitin at the crossroads of gene activation, cell death, inflammation, and cancer. Walczak H. Immunol. Rev. 244 9-28 (2011)
  69. The role of tumor necrosis factor receptor superfamily members in mammalian brain development, function and homeostasis. Twohig JP, Cuff SM, Yong AA, Wang EC. Rev Neurosci 22 509-533 (2011)
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  71. Sequence, structure, function, immunity: structural genomics of costimulation. Chattopadhyay K, Lazar-Molnar E, Yan Q, Rubinstein R, Zhan C, Vigdorovich V, Ramagopal UA, Bonanno J, Nathenson SG, Almo SC. Immunol. Rev. 229 356-386 (2009)
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  73. Tumour necrosis factor antagonists: structure, function, and tuberculosis risks. Wallis RS. Lancet Infect Dis 8 601-611 (2008)
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  86. The molecular architecture of the TNF superfamily. Bodmer JL, Schneider P, Tschopp J. Trends Biochem. Sci. 27 19-26 (2002)
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  92. TNF-related ligands and their receptors. Orlinick JR, Chao MV. Cell. Signal. 10 543-551 (1998)
  93. Getting it together: signal transduction in G-protein coupled receptors by association of receptor domains. Underwood DJ, Prendergast K. Chem. Biol. 4 239-248 (1997)
  94. Three-dimensional structures of proteins involved in programmed cell death. Liang H, Fesik SW. J. Mol. Biol. 274 291-302 (1997)
  95. The potential of combinatorial peptide libraries for the identification of inhibitors of TNF-alpha mediated cytotoxicity in vitro. Partidos CD, Chirinos-Rojas CL, Steward MW. Immunol. Lett. 57 113-116 (1997)
  96. Immune regulation by CD40 and its ligand GP39. Foy TM, Aruffo A, Bajorath J, Buhlmann JE, Noelle RJ. Annu. Rev. Immunol. 14 591-617 (1996)
  97. The TNF-ligand and receptor superfamilies: controllers of immunity and the Trojan horses of autoimmune disease? Hill CM, Lunec J. Mol. Aspects Med. 17 455-509 (1996)
  98. Molecular, structural, and biological characteristics of the tumor necrosis factor ligand superfamily. Gruss HJ. Int. J. Clin. Lab. Res. 26 143-159 (1996)
  99. A family of ligands for the TNF receptor superfamily. Cosman D. Stem Cells 12 440-455 (1994)
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  101. Animal models for reactive amyloidosis. Gruys E, Snel FW. Baillieres Clin Rheumatol 8 599-611 (1994)
  102. Knowledge-based model building of proteins: concepts and examples. Bajorath J, Stenkamp R, Aruffo A. Protein Sci. 2 1798-1810 (1993)
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  104. Tumor necrosis factor activities and cancer therapy--a perspective. Sidhu RS, Bollon AP. Pharmacol. Ther. 57 79-128 (1993)
  105. Cytokines: from clone to clinic. Aggarwal BB, Pocsik E. Arch. Biochem. Biophys. 292 335-359 (1992)
  106. Inflammatory cytokines. Cerami A. Clin. Immunol. Immunopathol. 62 S3-10 (1992)
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  108. Protein targets for structure-based drug design. Walkinshaw MD. Med Res Rev 12 317-372 (1992)
  109. Structure of tumor necrosis factor and its receptor. Aggarwal BB. Biotherapy 3 113-120 (1991)
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  112. Cytokines: an overview. Trotta PP. Am. J. Reprod. Immunol. 25 137-141 (1991)
  113. Lymphokine signal transduction. Guy GR, Bee NS, Peng CS. Prog. Growth Factor Res. 2 45-70 (1990)
  114. The divergent receptors for TNF. Sprang SR. Trends Biochem. Sci. 15 366-368 (1990)

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