The principal aim of this study was to compare the folding of a death domain (DD) from human FADD (FADD DD), an all-helical protein with a complex Greek key topology, with the two other classes of protein studied in depth in this laboratory: spectrin domains, simple all-alpha three-helix bundles, and Ig-like domains, all-beta proteins with complex Greek key topology.19,20 The death domains provide an opportunity to study the interplay between formation of secondary structure and topology in protein folding. Death domains have six anti-parallel alpha helices, arranged in a Greek key topology, with helices 1, 5 and 6 grouped in an approximately orthogonal position above helices 2, 3 and 4 (Fig. 1).21 Human FADD comprises two domains from the DD superfamily, each approximately 100 amino acids; the C-terminal DD is the one studied here.