2n2j
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Solution structure of the EBNA-2 N-terminal Dimerization (END) domain from the Epstein-barr virus== | |
| + | <StructureSection load='2n2j' size='340' side='right'caption='[[2n2j]]' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[2n2j]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_herpesvirus_4_strain_B95-8 Human herpesvirus 4 strain B95-8]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2N2J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2N2J FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2n2j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2n2j OCA], [https://pdbe.org/2n2j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2n2j RCSB], [https://www.ebi.ac.uk/pdbsum/2n2j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2n2j ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://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> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Epstein-Barr virus (EBV) is a gamma-herpesvirus that may cause infectious mononucleosis in young adults. In addition, epidemiological and molecular evidence links EBV to the pathogenesis of lymphoid and epithelial malignancies. EBV has the unique ability to transform resting B cells into permanently proliferating, latently infected lymphoblastoid cell lines. Epstein-Barr virus nuclear antigen 2 (EBNA-2) is a key regulator of viral and cellular gene expression for this transformation process. The N-terminal region of EBNA-2 comprising residues 1-58 appears to mediate multiple molecular functions including self-association and transactivation. However, it remains to be determined if the N-terminus of EBNA-2 directly provides these functions or if these activities merely depend on the dimerization involving the N-terminal domain. To address this issue, we determined the three-dimensional structure of the EBNA-2 N-terminal dimerization (END) domain by heteronuclear NMR-spectroscopy. The END domain monomer comprises a small fold of four beta-strands and an alpha-helix which form a parallel dimer by interaction of two beta-strands from each protomer. A structure-guided mutational analysis showed that hydrophobic residues in the dimer interface are required for self-association in vitro. Importantly, these interface mutants also displayed severely impaired self-association and transactivation in vivo. Moreover, mutations of solvent-exposed residues or deletion of the alpha-helix do not impair dimerization but strongly affect the functional activity, suggesting that the EBNA-2 dimer presents a surface that mediates functionally important intra- and/or intermolecular interactions. Our study shows that the END domain is a novel dimerization fold that is essential for functional activity. Since this specific fold is a unique feature of EBNA-2 it might provide a novel target for anti-viral therapeutics. | ||
| - | + | The EBNA-2 N-Terminal Transactivation Domain Folds into a Dimeric Structure Required for Target Gene Activation.,Friberg A, Thumann S, Hennig J, Zou P, Nossner E, Ling PD, Sattler M, Kempkes B PLoS Pathog. 2015 May 29;11(5):e1004910. doi: 10.1371/journal.ppat.1004910., eCollection 2015 May. PMID:26024477<ref>PMID:26024477</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Friberg | + | <div class="pdbe-citations 2n2j" style="background-color:#fffaf0;"></div> |
| - | [[Category: Sattler | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Human herpesvirus 4 strain B95-8]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Friberg A]] | ||
| + | [[Category: Sattler M]] | ||
Current revision
Solution structure of the EBNA-2 N-terminal Dimerization (END) domain from the Epstein-barr virus
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