Figure 2: Molecular modelling identifies two potential orientations for the FLIP–FADD interaction. | Nature Communications

Figure 2: Molecular modelling identifies two potential orientations for the FLIP–FADD interaction.

From: Differential affinity of FLIP and procaspase 8 for FADD’s DED binding surfaces regulates DISC assembly

Figure 2

(a) Homology model of human FLIP DED1 and DED2 (light and dark orange) superimposed on vFLIP X-ray protein (PDB id 2BBR; light green and green) and α3 region of FADD NMR-solved structure (PDB id 2GF5; dark green). The two DEDs (light and dark colours) are symmetrical and they are each composed of six α-helices. The human FLIP MC159 identity is 33%; the r.m.s.d. calculated on Cα atoms is 1.16 Å. (b) DED1/DED2 interactions within human FLIP. Hydrophobic interactions are centred on F23 located on α2 of DED1, which is accommodated into a hydrophobic groove between α1 and α4 of DED2. Two surfaces (α1/α4 and α2/α5) are involved in the intra- and intermolecular homotypic interactions between DEDs. On these surfaces, conserved hydrophobic residues are responsible for DED interactions: F on α2/α5 surface and (A)H/Y residues on α1/α4. Two possible orientations of FLIP/FADD interaction and their predicted docking energies are depicted: (c) F114 located on α2 helix of FLIP DED2 is accommodated into a hydrophobic groove formed between α1 and α4 helices of FADD DED; (d) F25 located on α2 helix of FADD DED is accommodated into an hydrophobic groove formed between α1 and α4 helices of FLIP DED1.

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