Structural basis of signal transduction in the TNF receptor superfamily

Adv Immunol. 2013:119:135-53. doi: 10.1016/B978-0-12-407707-2.00005-9.

Abstract

Members of the tumor necrosis factor receptor superfamily play key roles in innate and adaptive immunity. Here, we review recent structural studies in the intracellular signal transduction of these receptors. A central theme revealed from these structural studies is that upon ligand binding, multiple intracellular proteins form higher-order signaling machines to transduce and amplify receptor activation information to different cellular fates, including NF-κB activation, apoptosis, and programmed necrosis. These studies open a new vista for understanding the biophysical principles in these signaling cascades.

Keywords: Amyloid; Apoptosis; NF-κB; Necrosis; Structure; TNF.

Publication types

  • Review

MeSH terms

  • Apoptosis
  • Enzyme Activation
  • Humans
  • I-kappa B Kinase / chemistry
  • I-kappa B Kinase / metabolism
  • NF-kappa B / metabolism*
  • Necrosis
  • Protein Structure, Tertiary
  • Receptors, Tumor Necrosis Factor / chemistry
  • Receptors, Tumor Necrosis Factor / genetics
  • Receptors, Tumor Necrosis Factor / metabolism*
  • Signal Transduction*
  • Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / chemistry
  • Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • fas Receptor / metabolism

Substances

  • FAS protein, human
  • NF-kappa B
  • Receptors, Tumor Necrosis Factor
  • TNF protein, human
  • Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
  • Tumor Necrosis Factor-alpha
  • fas Receptor
  • I-kappa B Kinase