Crystal structure of Apaf-1 caspase recruitment domain: An alpha-helical Greek key fold for apoptotic signaling

The caspase recruitment domain (CARD) of Apaf-1 binds to the CARD of caspas e-9 to trigger a proteolytic cascade that leads to apoptotic cell death. We report the crystal structure of the Apaf-1 CARD at 1.3 Angstrom resolution , solved in a two-element multiwavelength anomalous dispersion (MAD) X-ray diffraction experiment. This CARD adopts a six-helix bundle fold with Creek key, topology surrounding an extensive hydrophobic core. This fold, which we call the "death fold", is found in other domains that mediate interactio ns in apoptotic signaling despite very low sequence identity. From a struct ure-based alignment, we identify conserved patterns that characterize the d eath fold and its subclasses. Like the Ig-fold, it provides:a rigid structu ral scaffold upon which diverse recognition surfaces are assembled. (C) 199 9 Academic Press.