View source for 2ypa


==Structure of the SCL:E47:LMO2:LDB1 complex bound to DNA==
<StructureSection load='2ypa' size='340' side='right'caption='[[2ypa]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2ypa]] 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=2YPA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2YPA 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]] 2.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=2ypa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ypa OCA], [https://pdbe.org/2ypa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ypa RCSB], [https://www.ebi.ac.uk/pdbsum/2ypa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ypa ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/TAL1_HUMAN TAL1_HUMAN] Precursor T-cell acute lymphoblastic leukemia. A chromosomal aberration involving TAL1 may be a cause of some T-cell acute lymphoblastic leukemias (T-ALL). Translocation t(1;14)(p32;q11) with T-cell receptor alpha chain (TCRA) genes.
== Function ==
[https://www.uniprot.org/uniprot/TAL1_HUMAN TAL1_HUMAN] Implicated in the genesis of hemopoietic malignancies. It may play an important role in hemopoietic differentiation. Serves as a positive regulator of erythroid differentiation (By similarity).<ref>PMID:1396592</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Cell fate is governed by combinatorial actions of transcriptional regulators assembling into multiprotein complexes. However, the molecular details of how these complexes form are poorly understood. One such complex, which contains the basic-helix-loop-helix heterodimer SCL:E47 and bridging proteins LMO2:LDB1, critically regulates hematopoiesis and induces T cell leukemia. Here, we report the crystal structure of (SCL:E47)bHLH:LMO2:LDB1LID bound to DNA, providing a molecular account of the network of interactions assembling this complex. This reveals an unexpected role for LMO2. Upon binding to SCL, LMO2 induces new hydrogen bonds in SCL:E47, thereby strengthening heterodimer formation. This imposes a rotation movement onto E47 that weakens the heterodimer:DNA interaction, shifting the main DNA-binding activity onto additional protein partners. Along with biochemical analyses, this illustrates, at an atomic level, how hematopoietic-specific SCL sequesters ubiquitous E47 and associated cofactors and supports SCL's reported DNA-binding-independent functions. Importantly, this work will drive the design of small molecules inhibiting leukemogenic processes.

Structural Basis for LMO2-Driven Recruitment of the SCL:E47bHLH Heterodimer to Hematopoietic-Specific Transcriptional Targets.,El Omari K, Hoosdally SJ, Tuladhar K, Karia D, Hall-Ponsele E, Platonova O, Vyas P, Patient R, Porcher C, Mancini EJ Cell Rep. 2013 Jul 11;4(1):135-47. doi: 10.1016/j.celrep.2013.06.008. Epub 2013, Jul 3. PMID:23831025<ref>PMID:23831025</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2ypa" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: El Omari K]]
[[Category: Hoosdally SJ]]
[[Category: Karia D]]
[[Category: Mancini EJ]]
[[Category: Patient R]]
[[Category: Platonova O]]
[[Category: Ponsele E]]
[[Category: Porcher C]]
[[Category: Tuladhar K]]
[[Category: Vyas P]]