The solution structure of FADD death domain. Structural basis of death domain interactions of Fas and FADD

J Biol Chem. 1999 Jun 4;274(23):16337-42. doi: 10.1074/jbc.274.23.16337.

Abstract

A signal of Fas-mediated apoptosis is transferred through an adaptor protein Fas-associated death domain protein (FADD) by interactions between the death domains of Fas and FADD. To understand the signal transduction mechanism of Fas-mediated apoptosis, we solved the solution structure of a murine FADD death domain. It consists of six helices arranged in a similar fold to the other death domains. The interactions between the death domains of Fas and FADD analyzed by site-directed mutagenesis indicate that charged residues in helices alpha2 and alpha3 are involved in death domain interactions, and the interacting helices appear to interact in anti-parallel pattern, alpha2 of FADD with alpha3 of Fas and vice versa.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Amino Acid Sequence
  • Animals
  • Apoptosis*
  • Binding Sites
  • Carrier Proteins / chemistry*
  • Carrier Proteins / metabolism*
  • Fas-Associated Death Domain Protein
  • Humans
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Peptide Fragments / chemistry
  • Protein Conformation
  • Sequence Alignment
  • Solutions
  • Structure-Activity Relationship
  • fas Receptor / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • FADD protein, human
  • Fadd protein, mouse
  • Fas-Associated Death Domain Protein
  • Peptide Fragments
  • Solutions
  • fas Receptor

Associated data

  • PDB/1FAD
  • PDB/R1FADMR