Fig. 5. cFLIP targets the CBS of the FADD-Casp-8 intermediate complex and further caps it.

a Thick orange lines highlight the CBS of the single-FADD intermediate complex shown in 2D representation. The CBS is targeted by cFLIP^tDED molecule CFk, as the first step of cFLIP recruitment. b Thick orange lines highlight the CBS generated after the recruitment of cFLIP^tDED molecule CFk to the single-FADD complex. The CBS could recruit another cFLIP^tDED molecule CFj. This process repeats until the complex is capped by cFLIP and reaches a maximum capacity of four cFLIP molecules. c Shows FADD^DED-cFLIP^tDED and Casp-8^tDED-cFLIP^tDED assemblies in the single-FADD complex. Surface representations of the single-FADD intermediate complex viewed from different angles show that the CBS contains a type Ia surface (yellow) from Casp-8^tDED molecule C8c DED1, a type IIa surface (orange) from Casp-8^tDED molecule C8d DED1, a type IIa (black) and a type IIIa (red) surfaces from FADD^DED molecule FAl, and a type IIIa surface (red) from Casp-8^tDED molecule C8a DED2. Red balls in the middle panel indicate the possible locations of the protease domains. d The pink box highlights FADD^DED-cFLIP^tDED and Casp-8^tDED-cFLIP^tDED interactions in c. cFLIP^tDED molecule CFk is shown as pink ribbons, while its interface residues are shown as sticks. In c–e, FADD^DED and Casp-8^tDED are labeled and colored as in Fig. 2a, except that FADD^DED molecule FAl is colored in white for clarity and for the comparison with the white Casp-8^tDED molecule in f. e The pink box highlights the corresponding CBS surfaces in the triple-FADD intermediate complex. Notably, two type IIa surfaces (black) are from FADD^DED molecules FAl and FAr. f, The corresponding CBS surfaces in the C8 filament (5L08 [10.2210/pdb5L08/pdb])³⁸. White surfaces highlight the C8 molecule that provides two type IIa (black and orange) and a type IIIa (red) surfaces.