2uzk

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of the human FOXO3a-DBD bound to DNA

Structural highlights

2uzk is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.7Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

FOXO3_HUMAN Note=A chromosomal aberration involving FOXO3 is found in secondary acute leukemias. Translocation t(6;11)(q21;q23) with MLL/HRX.

Function

FOXO3_HUMAN Transcriptional activator which triggers apoptosis in the absence of survival factors, including neuronal cell death upon oxidative stress. Recognizes and binds to the DNA sequence 5'-[AG]TAAA[TC]A-3'. Participates in post-transcriptional regulation of MYC: following phosphorylation by MAPKAPK5, promotes induction of miR-34b and miR-34c expression, 2 post-transcriptional regulators of MYC that bind to the 3'UTR of MYC transcript and prevent its translation.^[1] ^[2] ^[3]

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

FOXO3a is a transcription factor of the FOXO family. The FOXO proteins participate in multiple signaling pathways, and their transcriptional activity is regulated by several post-translational mechanisms, including phosphorylation, acetylation and ubiquitination. Because these post-translational modification sites are located within the C-terminal basic region of the FOXO DNA-binding domain (FOXO-DBD), it is possible that these post-translational modifications could alter the DNA-binding characteristics. To understand how FOXO mediate transcriptional activity, we report here the 2.7 A crystal structure of the DNA-binding domain of FOXO3a (FOXO3a-DBD) bound to a 13-bp DNA duplex containing a FOXO consensus binding sequence (GTAAACA). Based on a unique structural feature in the C-terminal region and results from biochemical and mutational studies, our studies may explain how FOXO-DBD C-terminal phosphorylation by protein kinase B (PKB) or acetylation by cAMP-response element binding protein (CBP) can attenuate the DNA-binding activity and thereby reduce transcriptional activity of FOXO proteins. In addition, we demonstrate that the methyl groups of specific thymine bases within the consensus sequence are important for FOXO3a-DBD recognition of the consensus binding site.

Crystal structure of the human FOXO3a-DBD/DNA complex suggests the effects of post-translational modification.,Tsai KL, Sun YJ, Huang CY, Yang JY, Hung MC, Hsiao CD Nucleic Acids Res. 2007;35(20):6984-94. Epub 2007 Oct 16. PMID:17940099^[4]

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

References

↑ Brunet A, Bonni A, Zigmond MJ, Lin MZ, Juo P, Hu LS, Anderson MJ, Arden KC, Blenis J, Greenberg ME. Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell. 1999 Mar 19;96(6):857-68. PMID:10102273
↑ Lehtinen MK, Yuan Z, Boag PR, Yang Y, Villen J, Becker EB, DiBacco S, de la Iglesia N, Gygi S, Blackwell TK, Bonni A. A conserved MST-FOXO signaling pathway mediates oxidative-stress responses and extends life span. Cell. 2006 Jun 2;125(5):987-1001. PMID:16751106 doi:S0092-8674(06)00559-9
↑ Kress TR, Cannell IG, Brenkman AB, Samans B, Gaestel M, Roepman P, Burgering BM, Bushell M, Rosenwald A, Eilers M. The MK5/PRAK kinase and Myc form a negative feedback loop that is disrupted during colorectal tumorigenesis. Mol Cell. 2011 Feb 18;41(4):445-57. doi: 10.1016/j.molcel.2011.01.023. PMID:21329882 doi:10.1016/j.molcel.2011.01.023
↑ Tsai KL, Sun YJ, Huang CY, Yang JY, Hung MC, Hsiao CD. Crystal structure of the human FOXO3a-DBD/DNA complex suggests the effects of post-translational modification. Nucleic Acids Res. 2007;35(20):6984-94. Epub 2007 Oct 16. PMID:17940099 doi:gkm703

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 See Also
7 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2uzk"

@@ Line 3: / Line 3: @@
 <StructureSection load='2uzk' size='340' side='right'caption='[[2uzk]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2uzk]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2UZK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2UZK FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2uzk]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2UZK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2UZK FirstGlance]. <br>
-</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2uzk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2uzk OCA], [https://pdbe.org/2uzk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2uzk RCSB], [https://www.ebi.ac.uk/pdbsum/2uzk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2uzk ProSAT]</span></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7&#8491;</td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2uzk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2uzk OCA], [https://pdbe.org/2uzk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2uzk RCSB], [https://www.ebi.ac.uk/pdbsum/2uzk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2uzk ProSAT]</span></td></tr>
 </table>
+== Disease ==
+[https://www.uniprot.org/uniprot/FOXO3_HUMAN FOXO3_HUMAN] Note=A chromosomal aberration involving FOXO3 is found in secondary acute leukemias. Translocation t(6;11)(q21;q23) with MLL/HRX.
+== Function ==
+[https://www.uniprot.org/uniprot/FOXO3_HUMAN FOXO3_HUMAN] Transcriptional activator which triggers apoptosis in the absence of survival factors, including neuronal cell death upon oxidative stress. Recognizes and binds to the DNA sequence 5'-[AG]TAAA[TC]A-3'. Participates in post-transcriptional regulation of MYC: following phosphorylation by MAPKAPK5, promotes induction of miR-34b and miR-34c expression, 2 post-transcriptional regulators of MYC that bind to the 3'UTR of MYC transcript and prevent its translation.<ref>PMID:10102273</ref> <ref>PMID:16751106</ref> <ref>PMID:21329882</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 32: / Line 37: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Hsiao, C D]]
+[[Category: Hsiao C-D]]
-[[Category: Huang, C Y]]
+[[Category: Huang C-Y]]
-[[Category: Hung, M C]]
+[[Category: Hung M-C]]
-[[Category: Sun, Y J]]
+[[Category: Sun Y-J]]
-[[Category: Tsai, K L]]
+[[Category: Tsai K-L]]
-[[Category: Yang, J Y]]
+[[Category: Yang J-Y]]
-[[Category: Activator]]
-[[Category: Apoptosis]]
-[[Category: Chromosomal rearrangement]]
-[[Category: Dna-binding]]
-[[Category: Dna-binding domain]]
-[[Category: Forkhead transcription factor]]
-[[Category: Nuclear protein]]
-[[Category: Phosphorylation]]
-[[Category: Proto-oncogene]]
-[[Category: Transcription]]
-[[Category: Transcription regulation]]
-[[Category: Winged helix]]

2uzk

From Proteopedia

Current revision

Crystal structure of the human FOXO3a-DBD bound to DNA

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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