Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Sci. Signal., 16 November 2010
Vol. 3, Issue 148, p. ra83
[DOI: 10.1126/scisignal.2000954]

RESEARCH ARTICLES

Editor's Summary

Structural Differences
The proinflammatory cytokine tumor necrosis factor (TNF) functions in the immune response; however, TNF also plays a pathophysiological role in diseases such as rheumatoid arthritis and Crohn’s disease. The effects of TNF are mediated by TNF receptor 1 (TNFR1) and TNFR2; whereas TNFR1 is ubiquitously expressed, TNFR2 is mostly restricted to cells of the immune system. Currently available therapies that block TNF include monoclonal antibodies against TNF and a soluble form of TNFR2; however, these therapies can result in serious side effects, some of which may be due to their nonselective effects. Here, Mukai et al. solved the structure of TNF in complex with TNFR2 and found differences between the ligand-binding interface of TNFR2 and that of TNFR1, whose structure is known. The authors also observed the formation of TNF-TNFR2 aggregates on the surface of transfected cells, which may be required for signal initiation. Solution of the TNFR2 structure may aid in the development of receptor-specific therapies.

Citation: Y. Mukai, T. Nakamura, M. Yoshikawa, Y. Yoshioka, S.-i. Tsunoda, S. Nakagawa, Y. Yamagata, Y. Tsutsumi, Solution of the Structure of the TNF-TNFR2 Complex. Sci. Signal. 3, ra83 (2010).

Read the Full Text

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Structural Basis for Treating Tumor Necrosis Factor {alpha} (TNF{alpha})-associated Diseases with the Therapeutic Antibody Infliximab.
S. Liang, J. Dai, S. Hou, L. Su, D. Zhang, H. Guo, S. Hu, H. Wang, Z. Rao, Y. Guo, et al. (2013)
J. Biol. Chem. 288, 13799-13807
   Abstract »    Full Text »    PDF »
Reduced Inflammation and Lymphoid Tissue Immunopathology in Rhesus Macaques Receiving Anti-Tumor Necrosis Factor Treatment During Primary Simian Immunodeficiency Virus Infection.
B. Tabb, D. R. Morcock, C. M. Trubey, O. A. Quinones, X. P. Hao, J. Smedley, R. Macallister, M. Piatak Jr, L. D. Harris, M. Paiardini, et al. (2013)
The Journal of Infectious Disease 207, 880-892
   Abstract »    Full Text »    PDF »
The Tumor Necrosis Factor Receptor Stalk Regions Define Responsiveness to Soluble versus Membrane-Bound Ligand.
C. Richter, S. Messerschmidt, G. Holeiter, J. Tepperink, S. Osswald, A. Zappe, M. Branschadel, V. Boschert, D. A. Mann, P. Scheurich, et al. (2012)
Mol. Cell. Biol. 32, 2515-2529
   Abstract »    Full Text »    PDF »
Progranulin Resolves Inflammation.
H. Wu and R. M. Siegel (2011)
Science 332, 427-428
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882