View source for 8xh6


==Structure of EBV LMP1 dimer==
<StructureSection load='8xh6' size='340' side='right'caption='[[8xh6]], [[Resolution|resolution]] 3.52&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8xh6]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_gammaherpesvirus_4 Human gammaherpesvirus 4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8XH6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8XH6 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.52&#8491;</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=8xh6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8xh6 OCA], [https://pdbe.org/8xh6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8xh6 RCSB], [https://www.ebi.ac.uk/pdbsum/8xh6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8xh6 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/LMP1_EBVG LMP1_EBVG] Acts as a CD40 functional homolog to prevent apoptosis of infected B-lymphocytes and drive their proliferation. Functions as a constitutively active tumor necrosis factor receptor that induces the activation of several signaling pathways, including those of the NF-kappa-B family. LMP1 signaling leads to up-regulation of antiapoptotic proteins and provide growth signals in latently infected cells. Interacts with host UBE2I and subsequently affects the sumoylation state of several cellular proteins. For example, induces the sumoylation of host IRF7 thereby limiting its transcriptional activity and modulating the activation of innate immune responses. Inhibits also host IFN-alpha-stimulated STAT2 nuclear translocation and interferon-stimulated response element transcriptional activity by interacting with and inhibiting host TYK2. Induces SUMO expression during viral latency thereby dysregulating the host sumoylation processes.[UniProtKB:P03230]
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== Publication Abstract from PubMed ==
Latent membrane protein 1 (LMP1) is the primary oncoprotein of Epstein-Barr virus (EBV) and plays versatile roles in the EBV life cycle and pathogenesis. Despite decades of extensive research, the molecular basis for LMP1 folding, assembly, and activation remains unclear. Here, we report cryo-electron microscopy structures of LMP1 in two unexpected assemblies: a symmetric homodimer and a higher-order filamentous oligomer. LMP1 adopts a non-canonical and unpredicted fold that supports the formation of a stable homodimer through tight and antiparallel intermolecular packing. LMP1 dimers further assemble side-by-side into higher-order filamentous oligomers, thereby allowing the accumulation and specific organization of the flexible cytoplasmic tails for efficient recruitment of downstream factors. Super-resolution microscopy and cellular functional assays demonstrate that mutations at both dimeric and oligomeric interfaces disrupt LMP1 higher-order assembly and block multiple LMP1-mediated signaling pathways. Our research provides a framework for understanding the mechanism of LMP1 and for developing potential therapies targeting EBV-associated diseases.

Assembly and activation of EBV latent membrane protein 1.,Huang J, Zhang X, Nie X, Zhang X, Wang Y, Huang L, Geng X, Li D, Zhang L, Gao G, Gao P Cell. 2024 Jul 4:S0092-8674(24)00695-0. doi: 10.1016/j.cell.2024.06.021. PMID:38996527<ref>PMID:38996527</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 8xh6" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Human gammaherpesvirus 4]]
[[Category: Large Structures]]
[[Category: Gao P]]
[[Category: Huang JF]]