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The crystal structure of the mouse apoptosis-inducing factor AIF

Nature Structural Biology volume 9, pages 442–446 (2002)Cite this article

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 Å. 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 β-hairpin loop, which may be related to its apoptogenic functions.

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Figure 1: Overall structure of mouse AIF.
Figure 2: Structural details.
Figure 3: The crystallographic AIF dimer.

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Acknowledgements

We acknowledge A. González and A. Munro for helpful discussions, R. Nageotte for technical help with analytical ultracentrifugation, the European Synchrotron Radiation Facility for access to their installations and the Institut Pasteur, as well as ARC, for financial support to P.M.A. M.J.M. and M.O.L. were recipients of EMBO/ARC and FEBS postdoctoral fellowships, respectively.

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Author notes

  1. Santos A. Susin

    Present address: Laboratoire d'Apoptose et Système Immunitaire, CNRS URA 1961, Institut Pasteur, 25 rue du Dr. Roux, 75724, Paris, France

  2. Josef Penninger

    Present address: IMBA, Institute for Molecular Biotechnology of the Austrian Academy of Sciences, c/o Dr. Bohrgasse 7, 1030, Vienna, Austria

Authors and Affiliations

  1. Unité de Biochimie Structurale, CNRS URA 2185, Institut Pasteur, 25 rue du Dr. Roux, Paris, 75724, France

    María J. Maté, Miguel Ortiz-Lombardía, Brigitte Boitel, Ahmed Haouz, Diana Tello & Pedro M. Alzari

  2. CNRS UMR 1599, Institut Gustave Roussy, Pavillon de Recherche 1, 39 rue Camille Desmoulins, Villejuif, 94805, France

    Santos A. Susin & Guido Kroemer

  3. Departments of Medical Biophysics and Immunology, The AMGEN Institute and Ontario Cancer Institute, University of Toronto, 620 University Avenue, Toronto, M5G 2C1, Ontario, Canada

    Josef Penninger

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  1. María J. Maté
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Correspondence to Pedro M. Alzari.

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Maté, M., Ortiz-Lombardía, M., Boitel, B. et al. The crystal structure of the mouse apoptosis-inducing factor AIF. Nat Struct Mol Biol 9, 442–446 (2002). https://doi.org/10.1038/nsb793

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