The crystal structure of DR6 in complex with the amyloid precursor protein provides insight into death receptor activation

Genes Dev. 2015 Apr 15;29(8):785-90. doi: 10.1101/gad.257675.114. Epub 2015 Apr 2.

Abstract

The amyloid precursor protein (APP) has garnered considerable attention due to its genetic links to Alzheimer's disease. Death receptor 6 (DR6) was recently shown to bind APP via the protein extracellular regions, stimulate axonal pruning, and inhibit synapse formation. Here, we report the crystal structure of the DR6 ectodomain in complex with the E2 domain of APP and show that it supports a model for APP-induced dimerization and activation of cell surface DR6.

Keywords: amyloid precursor protein; crystal structure; death receptor 6; dimerization; signal activation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amyloid beta-Protein Precursor / chemistry*
  • Amyloid beta-Protein Precursor / metabolism*
  • Animals
  • Crystallization
  • Dimerization
  • HEK293 Cells
  • Humans
  • Mice
  • Models, Molecular*
  • Protein Binding
  • Protein Structure, Quaternary
  • Protein Structure, Tertiary
  • Receptors, Tumor Necrosis Factor / chemistry*
  • Receptors, Tumor Necrosis Factor / metabolism*
  • Signal Transduction

Substances

  • Amyloid beta-Protein Precursor
  • Receptors, Tumor Necrosis Factor
  • Tnfrsf21 protein, mouse