Fig. 2. Functional domain organization of AIF. (a) Domains of AIF important for its oxidoreductase function. The FAD-binding and NADH-binding domains of AIF are depicted. In addition, an AIF-specific insertion (509-559) not found in other proteins of this family has been marked. Residues whose mutation affect FAD binding (Lys176, Glu313, Cus255-Gly260) are indicated. (b) Domains of AIF important for its apoptogenic function. Amino acids with positive charges exposed at the surface are indicated. The surface-exposed area of AIF recognized by a neutralizing antibody (151-200) is also marked. Gain-of-function mutations are indicated in blue, while loss-of-function mutations are in red. Note that this model has been built on the crystal structure of mouse AIF, while data on gain-of-function and loss-of-function mutations of positively charged surface arginines and lysines have been obtained from human AIF.