The crystal structure of the mouse apoptosis-inducing factor AIF.
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.
Maté
María J
MJ
Unité de Biochimie Structurale, CNRS URA 2185, Institut Pasteur, 25 rue du Dr. Roux, 75724 Paris, France.
Ortiz-Lombardía
Miguel
M
Boitel
Brigitte
B
Haouz
Ahmed
A
Tello
Diana
D
Susin
Santos A
SA
Penninger
Josef
J
Kroemer
Guido
G
Alzari
Pedro M
PM
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
D051033:Apoptosis Inducing Factor; D005420:Flavoproteins; D008565:Membrane Proteins; C494830:AIFM1 protein, mouse; D009243:NAD; D005182:Flavin-Adenine Dinucleotide