View source for 1e50


==AML1/CBFbeta complex==
<StructureSection load='1e50' size='340' side='right'caption='[[1e50]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1e50]] is a 10 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=1E50 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1E50 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6&#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=1e50 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1e50 OCA], [https://pdbe.org/1e50 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1e50 RCSB], [https://www.ebi.ac.uk/pdbsum/1e50 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1e50 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/RUNX1_HUMAN RUNX1_HUMAN] Note=A chromosomal aberration involving RUNX1/AML1 is a cause of M2 type acute myeloid leukemia (AML-M2). Translocation t(8;21)(q22;q22) with RUNX1T1.<ref>PMID:1423235</ref> <ref>PMID:8353289</ref> <ref>PMID:8334990</ref> <ref>PMID:7919324</ref> <ref>PMID:7541640</ref>   Note=A chromosomal aberration involving RUNX1/AML1 is a cause of therapy-related myelodysplastic syndrome (T-MDS). Translocation t(3;21)(q26;q22) with EAP or MECOM.  Note=A chromosomal aberration involving RUNX1/AML1 is a cause of chronic myelogenous leukemia (CML). Translocation t(3;21)(q26;q22) with EAP or MECOM.  Note=A chromosomal aberration involving RUNX1/AML1 is found in childhood acute lymphoblastic leukemia (ALL). Translocation t(12;21)(p13;q22) with TEL. The translocation fuses the 3'-end of TEL to the alternate 5'-exon of AML-1H.  Note=A chromosomal aberration involving RUNX1 is found in acute leukemia. Translocation t(11,21)(q13;q22) that forms a MACROD1-RUNX1 fusion protein.  Defects in RUNX1 are the cause of familial platelet disorder with associated myeloid malignancy (FPDMM) [MIM:[https://omim.org/entry/601399 601399]. FPDMM is an autosomal dominant disease characterized by qualitative and quantitative platelet defects, and propensity to develop acute myelogenous leukemia.<ref>PMID:10508512</ref>   Note=A chromosomal aberration involving RUNX1/AML1 is found in therapy-related myeloid malignancies. Translocation t(16;21)(q24;q22) that forms a RUNX1-CBFA2T3 fusion protein.  Note=A chromosomal aberration involving RUNX1/AML1 is a cause of chronic myelomonocytic leukemia. Inversion inv(21)(q21;q22) with USP16.
== Function ==
[https://www.uniprot.org/uniprot/RUNX1_HUMAN RUNX1_HUMAN] CBF binds to the core site, 5'-PYGPYGGT-3', of a number of enhancers and promoters, including murine leukemia virus, polyomavirus enhancer, T-cell receptor enhancers, LCK, IL-3 and GM-CSF promoters. The alpha subunit binds DNA and appears to have a role in the development of normal hematopoiesis. Isoform AML-1L interferes with the transactivation activity of RUNX1. Acts synergistically with ELF4 to transactivate the IL-3 promoter and with ELF2 to transactivate the mouse BLK promoter. Inhibits KAT6B-dependent transcriptional activation.<ref>PMID:10207087</ref> <ref>PMID:11965546</ref> <ref>PMID:14970218</ref> <ref>PMID:17431401</ref> 
== 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/e5/1e50_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/main_output.php?pdb_ID=1e50 ConSurf].
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== Publication Abstract from PubMed ==
Mutations in the genes encoding the interacting proteins AML1 and CBFbeta are the most common genetic abnormalities in acute leukaemia, and congenital mutations in the related AML3 gene are associated with disorders of osteogenesis. Furthermore, the interaction of AML1 with CBFbeta is essential for haematopoiesis. We report the 2.6 A resolution crystal structure of the complex between the AML1 Runt domain and CBFbeta, which represents a paradigm for the mode of interaction of this highly conserved family of transcription factors. The structure demonstrates that point mutations associated with cleidocranial dysplasia map to the conserved heterodimer interface, suggesting a role for CBFbeta in osteogenesis, and reveals a potential protein interaction platform composed of conserved negatively charged residues on the surface of CBFbeta.

Structural basis for the heterodimeric interaction between the acute leukaemia-associated transcription factors AML1 and CBFbeta.,Warren AJ, Bravo J, Williams RL, Rabbitts TH EMBO J. 2000 Jun 15;19(12):3004-15. PMID:10856244<ref>PMID:10856244</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Core-binding factor|Core-binding factor]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Bravo J]]
[[Category: Rabbits TH]]
[[Category: Warren AJ]]
[[Category: Williams RL]]