1M6I

Crystal Structure of Apoptosis Inducing Factor (AIF)

Summary for 1M6I

• Entry DOI: 10.2210/pdb1m6i/pdb
• Related: 1GV4
• Descriptor: Programmed cell death protein 8, FLAVIN-ADENINE DINUCLEOTIDE (3 entities in total)
• Functional Keywords: apoptosis, aif, oxidoreductase
• Biological source: Homo sapiens (human)
• Cellular location: Mitochondrion intermembrane space: O95831
• Total number of polymer chains: 1
• Total formula weight: 54729.81

Authors

Ye, H.,Cande, C.,Stephanou, N.C.,Jiang, S.,Gurbuxani, S.,Larochette, N.,Daugas, E.,Garrido, C.,Kroemer, G.,Wu, H. (deposition date: 2002-07-16, release date: 2002-08-28, Last modification date: 2024-02-14)

Primary citation

Ye, H.,Cande, C.,Stephanou, N.C.,Jiang, S.,Gurbuxani, S.,Larochette, N.,Daugas, E.,Garrido, C.,Kroemer, G.,Wu, H.
DNA binding is required for the apoptogenic action of apoptosis inducing factor.
Nat.Struct.Biol., 9:680-684, 2002

PubMed Abstract: 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.

PubMed: 12198487
DOI: 10.1038/nsb836

Experimental method

X-RAY DIFFRACTION (1.8 Å)