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| | ==Uninhibited DNA-binding domain of the Ets transcription factor ERG== | | ==Uninhibited DNA-binding domain of the Ets transcription factor ERG== |
| - | <StructureSection load='4irg' size='340' side='right' caption='[[4irg]], [[Resolution|resolution]] 1.70Å' scene=''> | + | <StructureSection load='4irg' size='340' side='right'caption='[[4irg]], [[Resolution|resolution]] 1.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4irg]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IRG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IRG FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4irg]] is a 1 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=4IRG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IRG FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4irh|4irh]], [[4iri|4iri]]</td></tr> | + | </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=4irg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4irg OCA], [https://pdbe.org/4irg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4irg RCSB], [https://www.ebi.ac.uk/pdbsum/4irg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4irg ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ERG ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4irg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4irg OCA], [http://pdbe.org/4irg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4irg RCSB], [http://www.ebi.ac.uk/pdbsum/4irg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4irg ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/ERG_HUMAN ERG_HUMAN]] Defects in ERG are a cause of Ewing sarcoma (ES) [MIM:[http://omim.org/entry/612219 612219]]. A highly malignant, metastatic, primitive small round cell tumor of bone and soft tissue that affects children and adolescents. It belongs to the Ewing sarcoma family of tumors, a group of morphologically heterogeneous neoplasms that share the same cytogenetic features. They are considered neural tumors derived from cells of the neural crest. Ewing sarcoma represents the less differentiated form of the tumors. Note=A chromosomal aberration involving ERG is found in patients with Erwing sarcoma. Translocation t(21;22)(q22;q12) with EWSR1. Note=Chromosomal aberrations involving ERG have been found in acute myeloid leukemia (AML). Translocation t(16;21)(p11;q22) with FUS. Translocation t(X;21)(q25-26;q22) with ELF4. | + | [https://www.uniprot.org/uniprot/ERG_HUMAN ERG_HUMAN] Defects in ERG are a cause of Ewing sarcoma (ES) [MIM:[https://omim.org/entry/612219 612219]. A highly malignant, metastatic, primitive small round cell tumor of bone and soft tissue that affects children and adolescents. It belongs to the Ewing sarcoma family of tumors, a group of morphologically heterogeneous neoplasms that share the same cytogenetic features. They are considered neural tumors derived from cells of the neural crest. Ewing sarcoma represents the less differentiated form of the tumors. Note=A chromosomal aberration involving ERG is found in patients with Erwing sarcoma. Translocation t(21;22)(q22;q12) with EWSR1. Note=Chromosomal aberrations involving ERG have been found in acute myeloid leukemia (AML). Translocation t(16;21)(p11;q22) with FUS. Translocation t(X;21)(q25-26;q22) with ELF4. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ERG_HUMAN ERG_HUMAN]] Transcriptional regulator. May participate in transcriptional regulation through the recruitment of SETDB1 histone methyltransferase and subsequent modification of local chromatin structure. | + | [https://www.uniprot.org/uniprot/ERG_HUMAN ERG_HUMAN] Transcriptional regulator. May participate in transcriptional regulation through the recruitment of SETDB1 histone methyltransferase and subsequent modification of local chromatin structure. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Bushweller, J H]] | + | [[Category: Large Structures]] |
| - | [[Category: Cafiso, D S]] | + | [[Category: Bushweller JH]] |
| - | [[Category: Horanyi, P S]] | + | [[Category: Cafiso DS]] |
| - | [[Category: Pryor, E E]] | + | [[Category: Horanyi PS]] |
| - | [[Category: Regan, M C]] | + | [[Category: Pryor EE]] |
| - | [[Category: Sarver, J L]] | + | [[Category: Regan MC]] |
| - | [[Category: Dna binding protein]] | + | [[Category: Sarver JL]] |
| - | [[Category: Ets domain]]
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| - | [[Category: Winged helix-turn-helix]]
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| Structural highlights
Disease
ERG_HUMAN Defects in ERG are a cause of Ewing sarcoma (ES) [MIM:612219. A highly malignant, metastatic, primitive small round cell tumor of bone and soft tissue that affects children and adolescents. It belongs to the Ewing sarcoma family of tumors, a group of morphologically heterogeneous neoplasms that share the same cytogenetic features. They are considered neural tumors derived from cells of the neural crest. Ewing sarcoma represents the less differentiated form of the tumors. Note=A chromosomal aberration involving ERG is found in patients with Erwing sarcoma. Translocation t(21;22)(q22;q12) with EWSR1. Note=Chromosomal aberrations involving ERG have been found in acute myeloid leukemia (AML). Translocation t(16;21)(p11;q22) with FUS. Translocation t(X;21)(q25-26;q22) with ELF4.
Function
ERG_HUMAN Transcriptional regulator. May participate in transcriptional regulation through the recruitment of SETDB1 histone methyltransferase and subsequent modification of local chromatin structure.
Publication Abstract from PubMed
The Ets-Related Gene (ERG) belongs to the Ets family of transcription factors and is critically important for maintenance of the hematopoietic stem cell population. A chromosomal translocation observed in the majority of human prostate cancers leads to the aberrant overexpression of ERG. We have identified regions flanking the ERG Ets domain responsible for autoinhibition of DNA binding and solved crystal structures of uninhibited, autoinhibited, and DNA-bound ERG. NMR-based measurements of backbone dynamics show that uninhibited ERG undergoes substantial dynamics on the millisecond-to-microsecond timescale but autoinhibited and DNA-bound ERG do not. We propose a mechanism whereby the allosteric basis of ERG autoinhibition is mediated predominantly by the regulation of Ets-domain dynamics with only modest structural changes.
Structural and dynamic studies of the transcription factor ERG reveal DNA binding is allosterically autoinhibited.,Regan MC, Horanyi PS, Pryor EE Jr, Sarver JL, Cafiso DS, Bushweller JH Proc Natl Acad Sci U S A. 2013 Jul 29. PMID:23898196[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Regan MC, Horanyi PS, Pryor EE Jr, Sarver JL, Cafiso DS, Bushweller JH. Structural and dynamic studies of the transcription factor ERG reveal DNA binding is allosterically autoinhibited. Proc Natl Acad Sci U S A. 2013 Jul 29. PMID:23898196 doi:10.1073/pnas.1301726110
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