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PDBsum entry 1gv4
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Oxidoreductase
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PDB id
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1gv4
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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The crystal structure of the mouse apoptosis-Inducing factor aif.
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Authors
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M.J.Maté,
M.Ortiz-Lombardía,
B.Boitel,
A.Haouz,
D.Tello,
S.A.Susin,
J.Penninger,
G.Kroemer,
P.M.Alzari.
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Ref.
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Nat Struct Biol, 2002,
9,
442-446.
[DOI no: ]
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PubMed id
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Abstract
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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.
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Figure 1.
Figure 1. Overall structure of mouse AIF. a, Structural
comparison of AIF, GR and BphA4. FAD and NADH are shown in black
and cyan sticks, respectively. b, Crystallographic contacts in
AIF crystals. Monomers 2 and 3 form a crystallographic dimer
related by a two-fold axis. The Pro-rich C-terminal insertion is
stabilized by crystal contacts, as seen between monomers 1 and
2. c, Distribution of invariant residues (green) among mammalian
and D. discoideum AIFs in both faces of the monomer. The FAD
molecular surface is shown in magenta. The dimerization area is
marked and the two-fold axis is depicted by an arrow.
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Figure 3.
Figure 3. The crystallographic AIF dimer. The stereo view of
the surface of one crystallographic dimer is seen along the
z-axis, slightly away from the noncrystallographic two-fold
axis. The rendered surface is colored by electrostatic
potential. An arrowhead indicates the entrance of each
NADH-binding pocket.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Biol
(2002,
9,
442-446)
copyright 2002.
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