|
|
| Line 1: |
Line 1: |
| - | {{STRUCTURE_2knh| PDB=2knh | SCENE= }}
| + | ==The Solution structure of the eTAFH domain of AML1-ETO complexed with HEB peptide== |
| - | ===The Solution structure of the eTAFH domain of AML1-ETO complexed with HEB peptide===
| + | <StructureSection load='2knh' size='340' side='right' caption='[[2knh]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> |
| - | {{ABSTRACT_PUBMED_19204326}}
| + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[2knh]] is a 2 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=2KNH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2KNH FirstGlance]. <br> |
| | + | </td></tr><tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RUNX1T1, AML1T1, CBFA2T1, CDR, ETO, MTG8, ZMYND2 ([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=2knh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2knh OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2knh RCSB], [http://www.ebi.ac.uk/pdbsum/2knh PDBsum]</span></td></tr> |
| | + | <table> |
| | + | == Disease == |
| | + | [[http://www.uniprot.org/uniprot/MTG8_HUMAN MTG8_HUMAN]] Note=A chromosomal aberration involving RUNX1T1 is a cause of acute myeloid leukemia (AML-M2). Translocation t(8;21)(q22;q22) with RUNX1/AML1.<ref>PMID:8334990</ref> <ref>PMID:7541640</ref> <ref>PMID:8353289</ref> <ref>PMID:1423235</ref> Defects in RUNX1T1 may be a cause of colorectal cancer (CRC) [MIM:[http://omim.org/entry/114500 114500]]. |
| | + | == Function == |
| | + | [[http://www.uniprot.org/uniprot/MTG8_HUMAN MTG8_HUMAN]] Transcription regulator that excerts its function by binding to histone deacetylases and transcription factors. Can repress transactivation mediated by TCF12.<ref>PMID:10973986</ref> <ref>PMID:16803958</ref> [[http://www.uniprot.org/uniprot/HTF4_HUMAN HTF4_HUMAN]] Transcriptional regulator. Involved in the initiation of neuronal differentiation. Activates transcription by binding to the E box (5'-CANNTG-3'). |
| | + | == Evolutionary Conservation == |
| | + | [[Image:Consurf_key_small.gif|200px|right]] |
| | + | Check<jmol> |
| | + | <jmolCheckbox> |
| | + | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kn/2knh_consurf.spt"</scriptWhenChecked> |
| | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | + | <text>to colour the structure by Evolutionary Conservation</text> |
| | + | </jmolCheckbox> |
| | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf]. |
| | + | <div style="clear:both"></div> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | AML1-ETO is the chimeric protein product of the t(8;21) in acute myeloid leukemia. The ETO portion of the fusion protein includes the eTAFH domain, which is homologous to several TATA binding protein-associated factors (TAFs) and interacts with E proteins (E2A and HEB). It has been proposed that AML1-ETO-mediated silencing of E protein function might be important for t(8;21) leukemogenesis. Here, we determined the solution structure of a complex between the AML1-ETO eTAFH domain and an interacting peptide from HEB. On the basis of the structure, key residues in AML1-ETO for HEB association were mutated. These mutations do not impair the ability of AML1-ETO to enhance the clonogenic capacity of primary mouse bone marrow cells and do not eliminate its ability to repress proliferation or granulocyte differentiation. Therefore, the eTAFH-E protein interaction appears to contribute relatively little to the activity of AML1-ETO. |
| | | | |
| - | ==Disease==
| + | Structure of the AML1-ETO eTAFH domain-HEB peptide complex and its contribution to AML1-ETO activity.,Park S, Chen W, Cierpicki T, Tonelli M, Cai X, Speck NA, Bushweller JH Blood. 2009 Apr 9;113(15):3558-67. Epub 2009 Feb 9. PMID:19204326<ref>PMID:19204326</ref> |
| - | [[http://www.uniprot.org/uniprot/MTG8_HUMAN MTG8_HUMAN]] Note=A chromosomal aberration involving RUNX1T1 is a cause of acute myeloid leukemia (AML-M2). Translocation t(8;21)(q22;q22) with RUNX1/AML1.<ref>PMID:8334990</ref><ref>PMID:7541640</ref><ref>PMID:8353289</ref><ref>PMID:1423235</ref> Defects in RUNX1T1 may be a cause of colorectal cancer (CRC) [MIM:[http://omim.org/entry/114500 114500]].
| + | |
| | | | |
| - | ==Function==
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | [[http://www.uniprot.org/uniprot/MTG8_HUMAN MTG8_HUMAN]] Transcription regulator that excerts its function by binding to histone deacetylases and transcription factors. Can repress transactivation mediated by TCF12.<ref>PMID:10973986</ref><ref>PMID:16803958</ref> [[http://www.uniprot.org/uniprot/HTF4_HUMAN HTF4_HUMAN]] Transcriptional regulator. Involved in the initiation of neuronal differentiation. Activates transcription by binding to the E box (5'-CANNTG-3').
| + | </div> |
| - | | + | == References == |
| - | ==About this Structure== | + | <references/> |
| - | [[2knh]] is a 2 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=2KNH OCA].
| + | __TOC__ |
| - | | + | </StructureSection> |
| - | ==Reference==
| + | |
| - | <ref group="xtra">PMID:019204326</ref><references group="xtra"/><references/>
| + | |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| | [[Category: Bushweller, J H.]] | | [[Category: Bushweller, J H.]] |
| Structural highlights
2knh is a 2 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: | RUNX1T1, AML1T1, CBFA2T1, CDR, ETO, MTG8, ZMYND2 (Homo sapiens) |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Disease
[MTG8_HUMAN] Note=A chromosomal aberration involving RUNX1T1 is a cause of acute myeloid leukemia (AML-M2). Translocation t(8;21)(q22;q22) with RUNX1/AML1.[1] [2] [3] [4] Defects in RUNX1T1 may be a cause of colorectal cancer (CRC) [MIM:114500].
Function
[MTG8_HUMAN] Transcription regulator that excerts its function by binding to histone deacetylases and transcription factors. Can repress transactivation mediated by TCF12.[5] [6] [HTF4_HUMAN] Transcriptional regulator. Involved in the initiation of neuronal differentiation. Activates transcription by binding to the E box (5'-CANNTG-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
AML1-ETO is the chimeric protein product of the t(8;21) in acute myeloid leukemia. The ETO portion of the fusion protein includes the eTAFH domain, which is homologous to several TATA binding protein-associated factors (TAFs) and interacts with E proteins (E2A and HEB). It has been proposed that AML1-ETO-mediated silencing of E protein function might be important for t(8;21) leukemogenesis. Here, we determined the solution structure of a complex between the AML1-ETO eTAFH domain and an interacting peptide from HEB. On the basis of the structure, key residues in AML1-ETO for HEB association were mutated. These mutations do not impair the ability of AML1-ETO to enhance the clonogenic capacity of primary mouse bone marrow cells and do not eliminate its ability to repress proliferation or granulocyte differentiation. Therefore, the eTAFH-E protein interaction appears to contribute relatively little to the activity of AML1-ETO.
Structure of the AML1-ETO eTAFH domain-HEB peptide complex and its contribution to AML1-ETO activity.,Park S, Chen W, Cierpicki T, Tonelli M, Cai X, Speck NA, Bushweller JH Blood. 2009 Apr 9;113(15):3558-67. Epub 2009 Feb 9. PMID:19204326[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Miyoshi H, Kozu T, Shimizu K, Enomoto K, Maseki N, Kaneko Y, Kamada N, Ohki M. The t(8;21) translocation in acute myeloid leukemia results in production of an AML1-MTG8 fusion transcript. EMBO J. 1993 Jul;12(7):2715-21. PMID:8334990
- ↑ Era T, Asou N, Kunisada T, Yamasaki H, Asou H, Kamada N, Nishikawa S, Yamaguchi K, Takatsuki K. Identification of two transcripts of AML1/ETO-fused gene in t(8;21) leukemic cells and expression of wild-type ETO gene in hematopoietic cells. Genes Chromosomes Cancer. 1995 May;13(1):25-33. PMID:7541640
- ↑ Kozu T, Miyoshi H, Shimizu K, Maseki N, Kaneko Y, Asou H, Kamada N, Ohki M. Junctions of the AML1/MTG8(ETO) fusion are constant in t(8;21) acute myeloid leukemia detected by reverse transcription polymerase chain reaction. Blood. 1993 Aug 15;82(4):1270-6. PMID:8353289
- ↑ Nisson PE, Watkins PC, Sacchi N. Transcriptionally active chimeric gene derived from the fusion of the AML1 gene and a novel gene on chromosome 8 in t(8;21) leukemic cells. Cancer Genet Cytogenet. 1992 Oct 15;63(2):81-8. PMID:1423235
- ↑ Wood JD, Nucifora FC Jr, Duan K, Zhang C, Wang J, Kim Y, Schilling G, Sacchi N, Liu JM, Ross CA. Atrophin-1, the dentato-rubral and pallido-luysian atrophy gene product, interacts with ETO/MTG8 in the nuclear matrix and represses transcription. J Cell Biol. 2000 Sep 4;150(5):939-48. PMID:10973986
- ↑ Plevin MJ, Zhang J, Guo C, Roeder RG, Ikura M. The acute myeloid leukemia fusion protein AML1-ETO targets E proteins via a paired amphipathic helix-like TBP-associated factor homology domain. Proc Natl Acad Sci U S A. 2006 Jul 5;103(27):10242-7. Epub 2006 Jun 27. PMID:16803958
- ↑ Park S, Chen W, Cierpicki T, Tonelli M, Cai X, Speck NA, Bushweller JH. Structure of the AML1-ETO eTAFH domain-HEB peptide complex and its contribution to AML1-ETO activity. Blood. 2009 Apr 9;113(15):3558-67. Epub 2009 Feb 9. PMID:19204326 doi:10.1182/blood-2008-06-161307
|
