Fig. 4. FADD^DED-FADD^DED and FADD^DED-Casp-8^tDED assemblies in the intermediate complex.

a Shows that FADD^DED molecules FAl, FAr, and FAq assemble a right-handed trimer that binds a left-handed Casp-8^tDED trimer in the triple-FADD-Casp-8 intermediate complex. The molecules are labeled and colored as in Fig. 3a, b. FAq and FAr refer to FADD^DED (FA) with the chain ID q and r, respectively. b Shows the interface residues on type I FADD^DED-FADD^DED and FADD^DED-Casp-8^tDED interfaces. The green and pink boxes show the residues on the type I interfaces in the triple-FADD, i.e., the FAl-FAr-FAq assembly, while the purple box shows the interface residues between Casp-8^tDED molecule C8a and FADD^DED molecule FAl. The type Ia surfaces and corresponding ribbons of FADD^DED are colored in yellow. The interface residues of FADD^DED molecules FAl, FAr, and FAq are labeled in red, purple, and black, respectively. while those on Casp-8^tDED molecule C8a are labeled in black. c, d Black boxes and double-headed arrows highlight the CSSb-CSSa interaction between the Casp-8^tDED trimer (c) and FADD^DED trimer (d) of the triple-FADD complex. In d, type IIa and IIIa surfaces are colored in black and red, respectively, in which functionally important FADD residues K33 and E51 are highlighted in white. The size of each interface on FADD^DED is shown in parentheses. Notably, in c, the type Ib residues of Casp-8^tDED molecule C8a are labeled in black. e-f, Black boxes and double-headed arrows highlight the corresponding CSSb-CSSa interaction in the single-FADD complex, between the corresponding Casp-8^tDED trimer (e) and single-FADD-single-Casp-8 assembly (f) with similar orientations to the those in c and d, respectively. Notably, in f, Casp-8 surfaces are colored as in Fig. 3a, except that functionally important Casp-8 residues R33 and K148³⁸ have white surfaces.