1m6i: Difference between revisions

Revision as of 14:52, 21 February 2008

Crystal Structure of Apoptosis Inducing Factor (AIF)

OverviewOverview

The execution of apoptosis or programmed cell death comprises both caspase-dependent and caspase-independent processes. Apoptosis inducing factor (AIF) was identified as a major player in caspase-independent cell death. It induces chromatin condensation and initial DNA cleavage via an unknown molecular mechanism. Here we report the crystal structure of human AIF at 1.8 A resolution. The structure reveals the presence of a strong positive electrostatic potential at the AIF surface, although the calculated isoelectric point for the entire protein is neutral. We show that recombinant AIF interacts with DNA in a sequence-independent manner. In addition, in cells treated with an apoptotic stimulus, endogenous AIF becomes co-localized with DNA at an early stage of nuclear morphological changes. Structure-based mutagenesis shows that DNA-binding defective mutants of AIF fail to induce cell death while retaining nuclear translocation. The potential DNA-binding site identified from mutagenesis also coincides with computational docking of a DNA duplex. These observations suggest that AIF-induced nuclear apoptosis requires a direct interaction with DNA.

About this StructureAbout this Structure

1M6I is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.

ReferenceReference

DNA binding is required for the apoptogenic action of apoptosis inducing factor., Ye H, Cande C, Stephanou NC, Jiang S, Gurbuxani S, Larochette N, Daugas E, Garrido C, Kroemer G, Wu H, Nat Struct Biol. 2002 Sep;9(9):680-4. PMID:12198487

Page seeded by OCA on Thu Feb 21 13:51:59 2008

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OCA

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-[[Image:1m6i.gif|left|200px]]<br />
+[[Image:1m6i.gif|left|200px]]<br /><applet load="1m6i" size="350" color="white" frame="true" align="right" spinBox="true"
-<applet load="1m6i" size="450" color="white" frame="true" align="right" spinBox="true"
 caption="1m6i, resolution 1.8&Aring;" />
 '''Crystal Structure of Apoptosis Inducing Factor (AIF)'''<br />
 ==Overview==
-The execution of apoptosis or programmed cell death comprises both, caspase-dependent and caspase-independent processes. Apoptosis inducing, factor (AIF) was identified as a major player in caspase-independent cell, death. It induces chromatin condensation and initial DNA cleavage via an, unknown molecular mechanism. Here we report the crystal structure of human, AIF at 1.8 A resolution. The structure reveals the presence of a strong, positive electrostatic potential at the AIF surface, although the, calculated isoelectric point for the entire protein is neutral. We show, that recombinant AIF interacts with DNA in a sequence-independent manner., In addition, in cells treated with an apoptotic stimulus, endogenous AIF, becomes co-localized with DNA at an early stage of nuclear morphological, changes. Structure-based mutagenesis shows that DNA-binding defective, mutants of AIF fail to induce cell death while retaining nuclear, translocation. The potential DNA-binding site identified from mutagenesis, also coincides with computational docking of a DNA duplex. These, observations suggest that AIF-induced nuclear apoptosis requires a direct, interaction with DNA.
+The execution of apoptosis or programmed cell death comprises both caspase-dependent and caspase-independent processes. Apoptosis inducing factor (AIF) was identified as a major player in caspase-independent cell death. It induces chromatin condensation and initial DNA cleavage via an unknown molecular mechanism. Here we report the crystal structure of human AIF at 1.8 A resolution. The structure reveals the presence of a strong positive electrostatic potential at the AIF surface, although the calculated isoelectric point for the entire protein is neutral. We show that recombinant AIF interacts with DNA in a sequence-independent manner. In addition, in cells treated with an apoptotic stimulus, endogenous AIF becomes co-localized with DNA at an early stage of nuclear morphological changes. Structure-based mutagenesis shows that DNA-binding defective mutants of AIF fail to induce cell death while retaining nuclear translocation. The potential DNA-binding site identified from mutagenesis also coincides with computational docking of a DNA duplex. These observations suggest that AIF-induced nuclear apoptosis requires a direct interaction with DNA.
 ==About this Structure==
-M6I is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with FAD as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1M6I OCA].
+M6I is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=FAD:'>FAD</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M6I OCA].
 ==Reference==
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 [[Category: Kroemer, G.]]
 [[Category: Larochette, N.]]
-[[Category: Stephanou, N.C.]]
+[[Category: Stephanou, N C.]]
 [[Category: Wu, H.]]
 [[Category: Ye, H.]]
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 [[Category: apoptosis]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 18:08:11 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:51:59 2008''