title: The crystal structure of the mouse apoptosis-inducing factor AIF.
abstract: Mitochondria play a key role in apoptosis due to their capacity to release potentially lethal proteins. One of these latent death factors is cytochrome c, which can stimulate the proteolytic activation of caspase zymogens. Another important protein is apoptosis-inducing factor (AIF), a flavoprotein that can stimulate a caspase-independent cell-death pathway required for early embryonic morphogenesis. Here, we report the crystal structure of mouse AIF at 2.0 A. Its active site structure and redox properties suggest that AIF functions as an electron transferase with a mechanism similar to that of the bacterial ferredoxin reductases, its closest evolutionary homologs. However, AIF structurally differs from these proteins in some essential features, including a long insertion in a C-terminal beta-hairpin loop, which may be related to its apoptogenic functions.
authors.affiliation: Unité de Biochimie Structurale, CNRS URA 2185, Institut Pasteur, 25 rue du Dr. Roux, 75724 Paris, France.
authors.forename: María J
authors.initials: MJ
authors.lastname: Maté
authors.forename: Miguel
authors.initials: M
authors.lastname: Ortiz-Lombardía
authors.forename: Brigitte
authors.initials: B
authors.lastname: Boitel
authors.forename: Ahmed
authors.initials: A
authors.lastname: Haouz
authors.forename: Diana
authors.initials: D
authors.lastname: Tello
authors.forename: Santos A
authors.initials: SA
authors.lastname: Susin
authors.forename: Josef
authors.initials: J
authors.lastname: Penninger
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
authors.forename: Pedro M
authors.initials: PM
authors.lastname: Alzari
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D017209:Apoptosis; D051033:Apoptosis Inducing Factor; D001665:Binding Sites; D018360:Crystallography, X-Ray; D019281:Dimerization; D004579:Electron Transport; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism; D005420:Flavoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D009243:NAD / Q000378:metabolism; D010084:Oxidation-Reduction; D011487:Protein Conformation; D017384:Sequence Deletion; D013329:Structure-Activity Relationship
chemical_list: D051033:Apoptosis Inducing Factor; D005420:Flavoproteins; D008565:Membrane Proteins; C494830:AIFM1 protein, mouse; D009243:NAD; D005182:Flavin-Adenine Dinucleotide