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| | <StructureSection load='5hda' size='340' side='right'caption='[[5hda]], [[Resolution|resolution]] 2.39Å' scene=''> | | <StructureSection load='5hda' size='340' side='right'caption='[[5hda]], [[Resolution|resolution]] 2.39Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5hda]] is a 4 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=5HDA OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5HDA FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5hda]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Human_herpesvirus_4_strain_B95-8 Human herpesvirus 4 strain B95-8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HDA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5HDA FirstGlance]. <br> |
| - | </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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3899Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ZMYND11, BRAM1, BS69 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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'>[http://proteopedia.org/fgij/fg.htm?mol=5hda FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hda OCA], [http://pdbe.org/5hda PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5hda RCSB], [http://www.ebi.ac.uk/pdbsum/5hda PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5hda 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=5hda FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hda OCA], [https://pdbe.org/5hda PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5hda RCSB], [https://www.ebi.ac.uk/pdbsum/5hda PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5hda ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ZMY11_HUMAN ZMY11_HUMAN]] Corepressor of transcription (Probable). May be involved in chromatin remodeling through association with several remodeling factors.<ref>PMID:16565076</ref> <ref>PMID:10734313</ref> [[http://www.uniprot.org/uniprot/EBNA2_EBVB9 EBNA2_EBVB9]] Plays a key role in the activation of the host resting B-cell and stimulation of B-cell proliferation. Acts by up-regulating the expression of viral EBNA1-6, LMP1, LMP2A and LMP2B genes, as well as several host genes including CD21, CD23 and MYC. Activates transcription by acting as an adapter molecule that binds to cellular sequence-specific DNA-binding proteins such as host CBF1, SMARCB1 and SPI1. Once EBNA2 is near promoter sites, its acidic activating domain recruits basal and activation-associated transcription factors TFIIB, TAF40, TFIIH components ERCC2 and ERCC3, and CBP in order to promote transcription. Alternatively, EBNA2 can affect activities of cell cycle regulators and retard cell cycle progression at G2/M phase. It also induces chromosomal instability, by disrupting mitotic checkpoints, multi-nucleation and formation of micronuclei in infected cells.<ref>PMID:19126642</ref> | + | [https://www.uniprot.org/uniprot/ZMY11_HUMAN ZMY11_HUMAN] Corepressor of transcription (Probable). May be involved in chromatin remodeling through association with several remodeling factors.<ref>PMID:16565076</ref> <ref>PMID:10734313</ref> |
| | <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: Human herpesvirus 4 strain B95-8]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Harter, M]] | + | [[Category: Harter M]] |
| - | [[Category: Song, J]] | + | [[Category: Song J]] |
| - | [[Category: Bs69]]
| + | |
| - | [[Category: Coiled-coil]]
| + | |
| - | [[Category: Ebna2]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Mynd]]
| + | |
| - | [[Category: Zmynd11]]
| + | |
| Structural highlights
Function
ZMY11_HUMAN Corepressor of transcription (Probable). May be involved in chromatin remodeling through association with several remodeling factors.[1] [2]
Publication Abstract from PubMed
Epstein-Barr virus (EBV) nuclear antigen 2 (EBNA2) plays an important role in driving immortalization of EBV-infected B cells through regulating the expression of many viral and cellular genes. We report a structural study of the tumor suppressor BS69/ZMYND11 C-terminal region, comprised of tandem coiled-coil-MYND domains (BS69CC-MYND), in complex with an EBNA2 peptide containing a PXLXP motif. The coiled-coil domain of BS69 self-associates to bring two separate MYND domains in close proximity, thereby enhancing the BS69 MYND-EBNA2 interaction. ITC analysis of BS69CC-MYND with a C-terminal fragment of EBNA2 further suggests that the BS69CC-MYND homodimer synergistically binds to the two EBNA2 PXLXP motifs that are respectively located in the conserved regions CR7 and CR8. Furthermore, we showed that EBNA2 interacts with BS69 and down-regulates its expression at both mRNA and protein levels in EBV-infected B cells. Ectopic BS69CC-MYND is recruited to viral target promoters through interactions with EBNA2, inhibits EBNA2-mediated transcription activation, and impairs proliferation of lymphoblastoid cell lines (LCLs). Substitution of critical residues in the MYND domain impairs the BS69-EBNA2 interaction and abolishes the BS69 inhibition of the EBNA2-mediated transactivation and LCL proliferation. This study identifies the BS69 C-terminal domains as an inhibitor of EBNA2, which may have important implications in development of novel therapeutic strategies against EBV infection.
BS69/ZMYND11 C-Terminal Domains Bind and Inhibit EBNA2.,Harter MR, Liu CD, Shen CL, Gonzalez-Hurtado E, Zhang ZM, Xu M, Martinez E, Peng CW, Song J PLoS Pathog. 2016 Feb 4;12(2):e1005414. doi: 10.1371/journal.ppat.1005414., eCollection 2016 Feb. PMID:26845565[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Velasco G, Grkovic S, Ansieau S. New insights into BS69 functions. J Biol Chem. 2006 Jun 16;281(24):16546-50. Epub 2006 Mar 24. PMID:16565076 doi:http://dx.doi.org/10.1074/jbc.M600573200
- ↑ Masselink H, Bernards R. The adenovirus E1A binding protein BS69 is a corepressor of transcription through recruitment of N-CoR. Oncogene. 2000 Mar 16;19(12):1538-46. PMID:10734313 doi:http://dx.doi.org/10.1038/sj.onc.1203421
- ↑ Harter MR, Liu CD, Shen CL, Gonzalez-Hurtado E, Zhang ZM, Xu M, Martinez E, Peng CW, Song J. BS69/ZMYND11 C-Terminal Domains Bind and Inhibit EBNA2. PLoS Pathog. 2016 Feb 4;12(2):e1005414. doi: 10.1371/journal.ppat.1005414., eCollection 2016 Feb. PMID:26845565 doi:http://dx.doi.org/10.1371/journal.ppat.1005414
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