Supplemental Data The Structure of FADD and Its Mode of Interaction with Procaspase-8 Paul E. Carrington, Cristinel Sandu, Yufeng Wei, Justine M. Hill, Gaku Morisawa, Ted Huang, Evridipis Gavathiotis, Yu Wei, and Milton H. Werner Supplemental Text: Calculation of the Structure of FADD Using a folding protocol within Xplor-NIH 2.12.2, a fully extended FADD molecule was folded using four different sets of input restraints: a) intra-domain NOEs, φ + ψ angles derived from analysis of chemical shifts with TALOS (Cornilescu et al., 1999) and 3 J NHα coupling constants; b) restraints from (a) plus inter-domain NOEs; c) restraints from (a) plus RDCs from Pf1 phage; d) restraints from (a) plus inter-domain NOEs plus RDCs from Pf1 phage. The structures resulting from sets (a) and (c) were similar to one another, as were the structures resulting from sets (b) and (d). Models from experiment (a) and (c) were immediately rejected, as they placed α6 and portions of the linker, residues 84-88, in direct contact with the death domain, yet no NOEs were observed that were consistent with this orientation of the linker and DD. Models from experiment (b) and (d) satisfied all of the experimental restraints in the input and were further refined to the same final orientation reported in Figure 1.