Structure of Apaf-1 in the auto-inhibited form: a critical role for ADP

Cell Cycle. 2005 Aug;4(8):1001-3. doi: 10.4161/cc.4.8.1849. Epub 2005 Aug 13.


The pathway of apoptosis is conserved in the three model species: mammals, Drosophila, and C. elegans. The apoptotic protease-activating factor 1, an essential protein conserved in all three species, is responsible for the activation of the initiator caspase-9 in mammalian cells. The structure of the auto-inhibited form of Apaf-1 reveals a critical role for ADP, which serves as an organizing center for four adjoining domains. The ADP-binding pocket contains features that are important for designing other nucleotide analogs. ATP binding is a prerequisite for the formation of the apoptosome. Despite strong sequence conservation between Apaf-1 and its orthologues in Drosophila and C. elegans, it is unclear whether they employ similar mechanisms for their own activation and for activating caspases. Much of the underlying mechanisms remain to be investigated by structural biology and biochemistry.

Publication types

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

MeSH terms

  • Adenosine Diphosphate / chemistry*
  • Adenosine Triphosphate / chemistry
  • Animals
  • Apoptosis*
  • Caenorhabditis elegans
  • Caspase 9
  • Caspases / metabolism
  • Drosophila Proteins / physiology*
  • Enzyme Inhibitors / pharmacology
  • Models, Molecular
  • Protein Conformation
  • Protein Structure, Secondary
  • Protein Structure, Tertiary


  • Drosophila Proteins
  • Enzyme Inhibitors
  • dark protein, Drosophila
  • Adenosine Diphosphate
  • Adenosine Triphosphate
  • Caspase 9
  • Caspases