1gv4

From Proteopedia

Murine apoptosis-inducing factor (AIF)

PDB ID 1gv4

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Structural highlights

1gv4 is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

AIFM1_MOUSE Functions both as NADH oxidoreductase and as regulator of apoptosis. In response to apoptotic stimuli, it is released from the mitochondrion intermembrane space into the cytosol and to the nucleus, where it functions as a proapoptotic factor in a caspase-independent pathway. In contrast, functions as an antiapoptotic factor in normal mitochondria via its NADH oxidoreductase activity. The soluble form (AIFsol) found in the nucleus induces 'parthanatos' i.e. caspase-independent fragmentation of chromosomal DNA. Interacts with EIF3G,and thereby inhibits the EIF3 machinery and protein synthesis,and activates casapse-7 to amplify apoptosis. Plays a critical role in caspase-independent, pyknotic cell death in hydrogen peroxide-exposed cells. Binds to DNA in a sequence-independent manner (By similarity).

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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.

The crystal structure of the mouse apoptosis-inducing factor AIF.,Mate MJ, Ortiz-Lombardia M, Boitel B, Haouz A, Tello D, Susin SA, Penninger J, Kroemer G, Alzari PM Nat Struct Biol. 2002 Jun;9(6):442-6. PMID:11967568^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Mate MJ, Ortiz-Lombardia M, Boitel B, Haouz A, Tello D, Susin SA, Penninger J, Kroemer G, Alzari PM. The crystal structure of the mouse apoptosis-inducing factor AIF. Nat Struct Biol. 2002 Jun;9(6):442-6. PMID:11967568 doi:10.1038/nsb793