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2k86

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Revision as of 13:17, 19 January 2015

Solution Structure of FOXO3a Forkhead domain

Structural highlights

2k86 is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	FOXO3, FKHRL1, FOXO3A (Homo sapiens)
Resources:	FirstGlance, OCA, RCSB, PDBsum

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, a forkhead transcription factor and member of the forkhead box class O (FOXO) subfamily, has been shown to promote the translocation of p53 to the cytoplasm, thereby inducing the mitochondria-associated apoptotic pathway. However, the binding sites that mediate this interaction between FOXO3a and p53 have not been identified. Here, we show that two regions within FOXO3a, the forkhead (FH) DNA binding domain and a conserved C-terminal transactivation domain (CR3), interact with the DNA binding domain of p53, with affinities in the low millimolar range and low micromolar range, respectively. Our data further suggest that within the FOXO3a molecule, the FH and CR3 domains engage in an intramolecular interaction with low micromolar affinity. Moreover, we used NMR to determine the solution structure of the FH domain. This enabled us to map the binding site for the CR3, which overlaps with the DNA binding site. We demonstrate that an intrinsically disordered linker between the FH and CR3 domains is required for full p53 binding activity. We also show that p53 disrupts the intramolecular interaction between FH and CR3. These results provide evidence for interplay of the FH and CR3 domains in association with p53.

Biochemical and structural characterization of an intramolecular interaction in FOXO3a and its binding with p53.,Wang F, Marshall CB, Yamamoto K, Li GY, Plevin MJ, You H, Mak TW, Ikura M J Mol Biol. 2008 Dec 19;384(3):590-603. Epub 2008 Sep 18. PMID:18824006^[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
↑ Wang F, Marshall CB, Yamamoto K, Li GY, Plevin MJ, You H, Mak TW, Ikura M. Biochemical and structural characterization of an intramolecular interaction in FOXO3a and its binding with p53. J Mol Biol. 2008 Dec 19;384(3):590-603. Epub 2008 Sep 18. PMID:18824006 doi:http://dx.doi.org/10.1016/j.jmb.2008.09.025

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2k86"

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[2k86]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2K86 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2K86 FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FOXO3, FKHRL1, FOXO3A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FOXO3, FKHRL1, FOXO3A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
-<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2k86 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k86 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2k86 RCSB], [http://www.ebi.ac.uk/pdbsum/2k86 PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2k86 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k86 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2k86 RCSB], [http://www.ebi.ac.uk/pdbsum/2k86 PDBsum]</span></td></tr>
-<table>
+</table>
 == Disease ==
 [[http://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.
@@ Line 28: / Line 28: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
-==See Also==
-*[[Forkhead box protein|Forkhead box protein]]
 == References ==
 <references/>
@@ Line 36: / Line 33: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Ikura, M.]]
+[[Category: Ikura, M]]
-[[Category: Li, G.]]
+[[Category: Li, G]]
-[[Category: Marshall, C B.]]
+[[Category: Marshall, C B]]
-[[Category: Plevin, M J.]]
+[[Category: Plevin, M J]]
-[[Category: Wang, F.]]
+[[Category: Wang, F]]
 [[Category: Activator]]
 [[Category: Apoptosis]]

2k86

From Proteopedia

Revision as of 13:17, 19 January 2015

Solution Structure of FOXO3a Forkhead domain

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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