1m6i
Crystal Structure of Apoptosis Inducing Factor (AIF)
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OverviewOverview
The execution of apoptosis or programmed cell death comprises both, caspase-dependent and caspase-independent processes. Apoptosis inducing, factor (AIF) was identified as a major player in caspase-independent cell, death. It induces chromatin condensation and initial DNA cleavage via an, unknown molecular mechanism. Here we report the crystal structure of human, AIF at 1.8 A resolution. The structure reveals the presence of a strong, positive electrostatic potential at the AIF surface, although the, calculated isoelectric point for the entire protein is neutral. We show, that recombinant AIF interacts with DNA in a sequence-independent manner., In addition, in cells treated with an apoptotic stimulus, endogenous AIF, becomes co-localized with DNA at an early stage of nuclear morphological, changes. Structure-based mutagenesis shows that DNA-binding defective, mutants of AIF fail to induce cell death while retaining nuclear, translocation. The potential DNA-binding site identified from mutagenesis, also coincides with computational docking of a DNA duplex. These, observations suggest that AIF-induced nuclear apoptosis requires a direct, interaction with DNA.
About this StructureAbout this Structure
1M6I is a Single protein structure of sequence from Homo sapiens with FAD as ligand. Full crystallographic information is available from OCA.
ReferenceReference
DNA binding is required for the apoptogenic action of apoptosis inducing factor., Ye H, Cande C, Stephanou NC, Jiang S, Gurbuxani S, Larochette N, Daugas E, Garrido C, Kroemer G, Wu H, Nat Struct Biol. 2002 Sep;9(9):680-4. PMID:12198487
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