Solution structure and mutagenesis of the caspase recruitment domain (CARD) from Apaf-1

Activation of procaspase-9, a key component of the apoptosis mechanism, req uires the interaction of its caspase recruitment domain (CARD) with the CAR D in the adaptor protein Apaf-1, Using nuclear magnetic resonance spectrosc opy and mutagenesis we have determined the structure of the CARD from Apaf- 1 and the residues important for binding the CARD in procaspase-9, Apaf-1's CARD contains seven short alpha-helices with the core six helices arranged in an antiparallel manner. Residues in helix 2 have a central role in medi ating interaction with procaspase-9 CARD, This interaction surface is disti nct from that proposed based on the structure of the CARD from RAIDD, but i s coincident with that of the structurally similar FADD death effector doma in and the Apaf-1 CARD interface identified by crystallographic studies.