|
|
| Line 3: |
Line 3: |
| | <StructureSection load='2ypb' size='340' side='right'caption='[[2ypb]], [[Resolution|resolution]] 2.87Å' scene=''> | | <StructureSection load='2ypb' size='340' side='right'caption='[[2ypb]], [[Resolution|resolution]] 2.87Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2ypb]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YPB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2YPB FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2ypb]] is a 4 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=2YPB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2YPB FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1hlh|1hlh]], [[2ypa|2ypa]]</div></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.87Å</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=2ypb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ypb OCA], [https://pdbe.org/2ypb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ypb RCSB], [https://www.ebi.ac.uk/pdbsum/2ypb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ypb ProSAT]</span></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=2ypb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ypb OCA], [https://pdbe.org/2ypb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ypb RCSB], [https://www.ebi.ac.uk/pdbsum/2ypb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ypb ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == 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. [[https://www.uniprot.org/uniprot/TFE2_HUMAN TFE2_HUMAN]] Precursor B-cell acute lymphoblastic leukemia. Chromosomal aberrations involving TCF3 are cause of forms of pre-B-cell acute lymphoblastic leukemia (B-ALL). Translocation t(1;19)(q23;p13.3) with PBX1. TCF3-PBX1 transforms cells by constitutively activating transcription of genes regulated by PBX1 or by other members of the PBX protein family. Translocation t(17;19)(q22;p13.3) with HLF. Inversion inv(19)(p13;q13) with TFPT.
| + | [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 == | | == 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> [[https://www.uniprot.org/uniprot/TFE2_HUMAN TFE2_HUMAN]] Transcriptional regulator. Involved in the initiation of neuronal differentiation. Heterodimers between TCF3 and tissue-specific basic helix-loop-helix (bHLH) proteins play major roles in determining tissue-specific cell fate during embryogenesis, like muscle or early B-cell differentiation. Dimers bind DNA on E-box motifs: 5'-CANNTG-3'. Binds to the kappa-E2 site in the kappa immunoglobulin gene enhancer. Binds to IEB1 and IEB2, which are short DNA sequences in the insulin gene transcription control region.
| + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 24: |
Line 24: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Hoosdally, S J]] | + | [[Category: El Omari K]] |
| - | [[Category: Karia, D]] | + | [[Category: Hoosdally SJ]] |
| - | [[Category: Mancini, E J]] | + | [[Category: Karia D]] |
| - | [[Category: Omari, K El]] | + | [[Category: Mancini EJ]] |
| - | [[Category: Patient, R]] | + | [[Category: Patient R]] |
| - | [[Category: Platonova, O]] | + | [[Category: Platonova O]] |
| - | [[Category: Ponsele, E]] | + | [[Category: Ponsele E]] |
| - | [[Category: Porcher, C]] | + | [[Category: Porcher C]] |
| - | [[Category: Tuladhar, K]] | + | [[Category: Tuladhar K]] |
| - | [[Category: Vyas, P]] | + | [[Category: Vyas P]] |
| - | [[Category: Hematopoiesis]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Leukemia]]
| + | |
| Structural highlights
Disease
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
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).[1]
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Aplan PD, Nakahara K, Orkin SH, Kirsch IR. The SCL gene product: a positive regulator of erythroid differentiation. EMBO J. 1992 Nov;11(11):4073-81. PMID:1396592
- ↑ El Omari K, Hoosdally SJ, Tuladhar K, Karia D, Hall-Ponsele E, Platonova O, Vyas P, Patient R, Porcher C, Mancini EJ. Structural Basis for LMO2-Driven Recruitment of the SCL:E47bHLH Heterodimer to Hematopoietic-Specific Transcriptional Targets. Cell Rep. 2013 Jul 11;4(1):135-47. doi: 10.1016/j.celrep.2013.06.008. Epub 2013, Jul 3. PMID:23831025 doi:10.1016/j.celrep.2013.06.008
|
