2h7b: Difference between revisions

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[[Image:2h7b.gif|left|200px]]
{{Seed}}
[[Image:2h7b.png|left|200px]]


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{{STRUCTURE_2h7b|  PDB=2h7b  |  SCENE=  }}  
{{STRUCTURE_2h7b|  PDB=2h7b  |  SCENE=  }}  


'''Solution structure of the eTAFH domain from the human leukemia-associated fusion protein AML1-ETO'''
===Solution structure of the eTAFH domain from the human leukemia-associated fusion protein AML1-ETO===




==Overview==
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Up to 15% of acute myeloid leukemias (AMLs) are characterized by the abnormal expression of the eight-twenty-one (ETO) transcriptional corepressor within an AML1-ETO fusion protein. The t(8;21) chromosomal translocation serves not only to disrupt WT AML1 function but also to introduce ETO activity during hematopoiesis. AML1-ETO was recently shown to inhibit E protein transactivation by physically displacing WT coactivator proteins in an interaction mediated by ETO. Here, we present the 3D solution structure of the human ETO TAFH (eTAFH) domain implicated in AML1-ETO:E protein interactions and report an unexpected fold similarity to paired amphipathic helix domains from the transcriptional corepressor Sin3. We identify and characterize a conserved surface on eTAFH that is essential for ETO:E protein recognition and show that the mutation of key conserved residues at this site alleviates ETO-based silencing of E protein transactivation. Our results address uncharacterized aspects of the corepression mechanism of ETO and suggest that eTAFH may serve to recruit ETO (or AML1-ETO) to DNA-bound transcription factors. Together, these findings imply that a cofactor exchange mechanism, analogous to that described for E protein inhibition, may represent a common mode of action for ETO.
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{{ABSTRACT_PUBMED_16803958}}


==About this Structure==
==About this Structure==
2H7B is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H7B OCA].  
2H7B is a [[Single protein]] structure of 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=2H7B OCA].  


==Reference==
==Reference==
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[[Category: Zhang, J.]]
[[Category: Zhang, J.]]
[[Category: 4 helix bundle]]
[[Category: 4 helix bundle]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 05:57:15 2008''
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 08:24:31 2008''

Revision as of 05:24, 29 July 2008

File:2h7b.png

Template:STRUCTURE 2h7b

Solution structure of the eTAFH domain from the human leukemia-associated fusion protein AML1-ETO

Template:ABSTRACT PUBMED 16803958

About this Structure

2H7B is a Single protein structure of sequence from Homo sapiens. Full experimental information is available from OCA.

Reference

The acute myeloid leukemia fusion protein AML1-ETO targets E proteins via a paired amphipathic helix-like TBP-associated factor homology domain., Plevin MJ, Zhang J, Guo C, Roeder RG, Ikura M, Proc Natl Acad Sci U S A. 2006 Jul 5;103(27):10242-7. Epub 2006 Jun 27. PMID:16803958

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