3alq Citations

Solution of the structure of the TNF-TNFR2 complex.


Tumor necrosis factor (TNF) is an inflammatory cytokine that has important roles in various immune responses, which are mediated through its two receptors, TNF receptor 1 (TNFR1) and TNFR2. Antibody-based therapy against TNF is used clinically to treat several chronic autoimmune diseases; however, such treatment sometimes results in serious side effects, which are thought to be caused by the blocking of signals from both TNFRs. Therefore, knowledge of the structural basis for the recognition of TNF by each receptor would be invaluable in designing TNFR-selective drugs. Here, we solved the 3.0 angstrom resolution structure of the TNF-TNFR2 complex, which provided insight into the molecular recognition of TNF by TNFR2. Comparison to the known TNFR1 structure highlighted several differences between the ligand-binding interfaces of the two receptors. Additionally, we also demonstrated that TNF-TNFR2 formed aggregates on the surface of cells, which may be required for signal initiation. These results may contribute to the design of therapeutics for autoimmune diseases.

Articles - 3alq mentioned but not cited (6)

  1. Interleukin-2 signalling is modulated by a labile disulfide bond in the CD132 chain of its receptor. Metcalfe C, Cresswell P, Barclay AN. Open Biol 2 110036 (2012)
  2. Solvent Selection for Insoluble Ligands, a Challenge for Biological Assay Development: A TNF-α/SPD304 Study. Papaneophytou CP, Mettou AK, Rinotas V, Douni E, Kontopidis GA. ACS Med Chem Lett 4 137-141 (2013)
  3. Generation and characterization of small single domain antibodies inhibiting human tumor necrosis factor receptor 1. Steeland S, Puimège L, Vandenbroucke RE, Van Hauwermeiren F, Haustraete J, Devoogdt N, Hulpiau P, Leroux-Roels G, Laukens D, Meuleman P, De Vos M, Libert C. J. Biol. Chem. 290 4022-4037 (2015)
  4. Exogenous TNFR2 activation protects from acute GvHD via host T reg cell expansion. Chopra M, Biehl M, Steinfatt T, Brandl A, Kums J, Amich J, Vaeth M, Kuen J, Holtappels R, Podlech J, Mottok A, Kraus S, Jordán-Garrote AL, Bäuerlein CA, Brede C, Ribechini E, Fick A, Seher A, Polz J, Ottmüller KJ, Baker J, Nishikii H, Ritz M, Mattenheimer K, Schwinn S, Winter T, Schäfer V, Krappmann S, Einsele H, Müller TD, Reddehase MJ, Lutz MB, Männel DN, Berberich-Siebelt F, Wajant H, Beilhack A. J. Exp. Med. 213 1881-1900 (2016)
  5. Exploring interaction of TNF and orthopoxviral CrmB protein by surface plasmon resonance and free energy calculation. Ivanisenko NV, Tregubchak TV, Saik OV, Ivanisenko VA, Shchelkunov SN. Protein Pept. Lett. 21 1273-1281 (2014)
  6. Using Molecular Docking Analysis to Discovery Dregea sinensis Hemsl. Potential Mechanism of Anticancer, Antidepression, and Immunoregulation. Liu X, Shi Y, Deng Y, Dai R. Pharmacogn Mag 13 358-362 (2017)

Reviews citing this publication (8)

  1. Piecing it together: Unraveling the elusive structure-function relationship in single-pass membrane receptors. Valley CC, Lewis AK, Sachs JN. Biochim. Biophys. Acta 1859 1398-1416 (2017)
  2. Understanding CD30 biology and therapeutic targeting: a historical perspective providing insight into future directions. van der Weyden CA, Pileri SA, Feldman AL, Whisstock J, Prince HM. Blood Cancer J 7 e603 (2017)
  3. Inflammatory osteolysis: a conspiracy against bone. Mbalaviele G, Novack DV, Schett G, Teitelbaum SL. J. Clin. Invest. 127 2030-2039 (2017)
  4. Biologics beyond TNF-α inhibitors and the effect of targeting the homologues TL1A-DR3 pathway in chronic inflammatory disorders. Tougaard P, Zervides KA, Skov S, Hansen AK, Pedersen AE. Immunopharmacol Immunotoxicol 38 29-38 (2016)
  5. Development of novel drug delivery systems using phage display technology for clinical application of protein drugs. Nagano K, Tsutsumi Y. Proc. Jpn. Acad., Ser. B, Phys. Biol. Sci. 92 156-166 (2016)
  6. Principles of antibody-mediated TNF receptor activation. Wajant H. Cell Death Differ. 22 1727-1741 (2015)
  7. Current approaches to fine mapping of antigen-antibody interactions. Abbott WM, Damschroder MM, Lowe DC. Immunology 142 526-535 (2014)
  8. Regulation of TNF-α with a focus on rheumatoid arthritis. Moelants EA, Mortier A, Van Damme J, Proost P. Immunol. Cell Biol. 91 393-401 (2013)

Articles citing this publication (31)

  1. Comparison of the inhibition mechanisms of adalimumab and infliximab in treating tumor necrosis factor α-associated diseases from a molecular view. Hu S, Liang S, Guo H, Zhang D, Li H, Wang X, Yang W, Qian W, Hou S, Wang H, Guo Y, Lou Z. J. Biol. Chem. 288 27059-27067 (2013)
  2. Medicine. Progranulin resolves inflammation. Wu H, Siegel RM. Science 332 427-428 (2011)
  3. Reduced inflammation and lymphoid tissue immunopathology in rhesus macaques receiving anti-tumor necrosis factor treatment during primary simian immunodeficiency virus infection. Tabb B, Morcock DR, Trubey CM, Quiñones OA, Hao XP, Smedley J, Macallister R, Piatak M, Harris LD, Paiardini M, Silvestri G, Brenchley JM, Alvord WG, Lifson JD, Estes JD. J. Infect. Dis. 207 880-892 (2013)
  4. Structural basis for treating tumor necrosis factor α (TNFα)-associated diseases with the therapeutic antibody infliximab. Liang S, Dai J, Hou S, Su L, Zhang D, Guo H, Hu S, Wang H, Rao Z, Guo Y, Lou Z. J. Biol. Chem. 288 13799-13807 (2013)
  5. Binding efficiency of protein-protein complexes. Day ES, Cote SM, Whitty A. Biochemistry 51 9124-9136 (2012)
  6. The tumor necrosis factor receptor stalk regions define responsiveness to soluble versus membrane-bound ligand. Richter C, Messerschmidt S, Holeiter G, Tepperink J, Osswald S, Zappe A, Branschädel M, Boschert V, Mann DA, Scheurich P, Krippner-Heidenreich A. Mol. Cell. Biol. 32 2515-2529 (2012)
  7. The crystal structure of death receptor 6 (DR6): a potential receptor of the amyloid precursor protein (APP). Kuester M, Kemmerzehl S, Dahms SO, Roeser D, Than ME. J. Mol. Biol. 409 189-201 (2011)
  8. Anti-TNF drives regulatory T cell expansion by paradoxically promoting membrane TNF-TNF-RII binding in rheumatoid arthritis. Nguyen DX, Ehrenstein MR. J. Exp. Med. 213 1241-1253 (2016)
  9. A protein disulfide isomerase/thioredoxin-1 complex is physically attached to exofacial membrane tumor necrosis factor receptors: overexpression in chronic lymphocytic leukemia cells. Söderberg A, Hossain A, Rosén A. Antioxid. Redox Signal. 18 363-375 (2013)
  10. A novel small-molecule tumor necrosis factor α inhibitor attenuates inflammation in a hepatitis mouse model. Ma L, Gong H, Zhu H, Ji Q, Su P, Liu P, Cao S, Yao J, Jiang L, Han M, Ma X, Xiong D, Luo HR, Wang F, Zhou J, Xu Y. J. Biol. Chem. 289 12457-12466 (2014)
  11. Dimerization of LTβR by LTα1β2 is necessary and sufficient for signal transduction. Sudhamsu J, Yin J, Chiang EY, Starovasnik MA, Grogan JL, Hymowitz SG. Proc. Natl. Acad. Sci. U.S.A. 110 19896-19901 (2013)
  12. Mechanistic basis for functional promiscuity in the TNF and TNF receptor superfamilies: structure of the LIGHT:DcR3 assembly. Liu W, Zhan C, Cheng H, Kumar PR, Bonanno JB, Nathenson SG, Almo SC. Structure 22 1252-1262 (2014)
  13. Three TNFR-binding domains of PGRN act independently in inhibition of TNF-alpha binding and activity. Tian Q, Zhao Y, Mundra JJ, Gonzalez-Gugel E, Jian J, Uddin SM, Liu C. Front Biosci (Landmark Ed) 19 1176-1185 (2014)
  14. The transmembrane domains of TNF-related apoptosis-inducing ligand (TRAIL) receptors 1 and 2 co-regulate apoptotic signaling capacity. Neumann S, Bidon T, Branschädel M, Krippner-Heidenreich A, Scheurich P, Doszczak M. PLoS ONE 7 e42526 (2012)
  15. Structural pathways of cytokines may illuminate their roles in regulation of cancer development and immunotherapy. Guven-Maiorov E, Acuner-Ozbabacan SE, Keskin O, Gursoy A, Nussinov R. Cancers (Basel) 6 663-683 (2014)
  16. Citrullination of TNF-α by peptidylarginine deiminases reduces its capacity to stimulate the production of inflammatory chemokines. Moelants EA, Mortier A, Grauwen K, Ronsse I, Van Damme J, Proost P. Cytokine 61 161-167 (2013)
  17. Manipulation of receptor oligomerization as a strategy to inhibit signaling by TNF superfamily members. Warren JT, Nelson CA, Decker CE, Zou W, Fremont DH, Teitelbaum SL. Sci Signal 7 ra80 (2014)
  18. Human and mouse CD137 have predominantly different binding CRDs to their respective ligands. Yi L, Zhao Y, Wang X, Dai M, Hellström KE, Hellström I, Zhang H. PLoS ONE 9 e86337 (2014)
  19. Comparative Biochemical and Functional Analysis of Viral and Human Secreted Tumor Necrosis Factor (TNF) Decoy Receptors. Pontejo SM, Alejo A, Alcami A. J. Biol. Chem. 290 15973-15984 (2015)
  20. A minimal mathematical model for the initial molecular interactions of death receptor signalling. Winkel C, Neumann S, Surulescu C, Scheurich P. Math Biosci Eng 9 663-683 (2012)
  21. Targeting TNFR2 with antagonistic antibodies inhibits proliferation of ovarian cancer cells and tumor-associated Tregs. Torrey H, Butterworth J, Mera T, Okubo Y, Wang L, Baum D, Defusco A, Plager S, Warden S, Huang D, Vanamee E, Foster R, Faustman DL. Sci Signal 10 (2017)
  22. TRAIL-based tumor sensitizing galactoxyloglucan, a novel entity for targeting apoptotic machinery. Aravind SR, Joseph MM, George SK, Dileep KV, Varghese S, Rose-James A, Balaram P, Sadasivan C, Sreelekha TT. Int. J. Biochem. Cell Biol. 59 153-166 (2015)
  23. Structural insights into the C1q domain of Caprin-2 in canonical Wnt signaling. Miao H, Jia Y, Xie S, Wang X, Zhao J, Chu Y, Zhou Z, Shi Z, Song X, Li L. J. Biol. Chem. 289 34104-34113 (2014)
  24. Molecular Basis for the Neutralization of Tumor Necrosis Factor α by Certolizumab Pegol in the Treatment of Inflammatory Autoimmune Diseases. Lee JU, Shin W, Son JY, Yoo KY, Heo YS. Int J Mol Sci 18 (2017)
  25. Conserved Fever Pathways across Vertebrates: A Herpesvirus Expressed Decoy TNF-α Receptor Delays Behavioral Fever in Fish. Rakus K, Ronsmans M, Forlenza M, Boutier M, Piazzon MC, Jazowiecka-Rakus J, Gatherer D, Athanasiadis A, Farnir F, Davison AJ, Boudinot P, Michiels T, Wiegertjes GF, Vanderplasschen A. Cell Host Microbe 21 244-253 (2017)
  26. Quantitative flow cytometric analysis of expression of tumor necrosis factor receptor types I and II on mononuclear cells. Lopatnikova JA, Vasilyev FF, Alshevskaya AA, Sennikov SV. J. Recept. Signal Transduct. Res. 33 49-55 (2013)
  27. Reconstructing the discontinuous and conformational β1/β3-loop binding site on hFSH/hCG by using highly constrained multicyclic peptides. Smeenk LE, Timmers-Parohi D, Benschop JJ, Puijk WC, Hiemstra H, van Maarseveen JH, Timmerman P. Chembiochem 16 91-99 (2015)
  28. Are different stoichiometries feasible for complexes between lymphotoxin-alpha and tumor necrosis factor receptor 1? Mascarenhas NM, Kästner J. BMC Struct. Biol. 12 8 (2012)
  29. Rational design of TNFα binding proteins based on the de novo designed protein DS119. Zhu C, Zhang C, Zhang T, Zhang X, Shen Q, Tang B, Liang H, Lai L. Protein Sci. 25 2066-2075 (2016)
  30. Analytical ultracentrifugation with fluorescence detection system reveals differences in complex formation between recombinant human TNF and different biological TNF antagonists in various environments. Krayukhina E, Noda M, Ishii K, Maruno T, Wakabayashi H, Tada M, Suzuki T, Ishii-Watabe A, Kato M, Uchiyama S. MAbs 9 664-679 (2017)
  31. Functionality of intrinsic disorder in tumor necrosis factor-α and its receptors. Uversky VN, El-Baky NA, El-Fakharany EM, Sabry A, Mattar EH, Uversky AV, Redwan EM. FEBS J. 284 3589-3618 (2017)