5t7x
From Proteopedia
Crystal structure of HHV-4 EBNA1 DNA binding domain (patient-derived, nasopharyngeal carcinoma) bound to DNA
Structural highlights
Function[EBNA1_EBVG] Plays an essential role in replication and partitioning of viral genomic DNA during latent viral infection. During this phase, the circular double-stranded viral DNA undergoes replication once per cell cycle and is efficiently partitioned to the daughter cells. EBNA1 activates the initiation of viral DNA replication through binding to specific sites in the viral latent origin of replication, oriP. Additionally, it governs the segregation of viral episomes by mediating their attachment to host cell metaphase chromosomes. Also activates the transcription of several viral latency genes. Finally, it can counteract the stabilization of host p53/TP53 by host USP7, thereby decreasing apoptosis and increasing host cell survival (By similarity). Publication Abstract from PubMedEpstein-Barr Virus (EBV) latent infection is a causative co-factor for endemic Nasopharyngeal Carcinoma (NPC). NPC-associated variants have been identified in EBV-encoded nuclear antigen EBNA1. Here, we solve the X-ray crystal structure of an NPC-derived EBNA1 DNA binding domain (DBD) and show that variant amino acids are found on the surface away from the DNA binding interface. We show that NPC-derived EBNA1 is compromised for DNA replication and episome maintenance functions. Recombinant virus containing the NPC EBNA1 DBD are impaired in their ability to immortalize primary B-lymphocytes and suppress lytic transcription during early stages of B-cell infection. We identify Survivin as a host protein deficiently bound by the NPC variant of EBNA1 and show that Survivin depletion compromises EBV episome maintenance in multiple cell types. We propose that endemic variants of EBNA1 play a significant role in EBV-driven carcinogenesis by altering key regulatory interactions that destabilize latent infection. Carcinoma-risk variant of EBNA1 deregulates Epstein-Barr Virus episomal latency.,Dheekollu J, Malecka K, Wiedmer A, Delecluse HJ, Chiang AK, Altieri DC, Messick TE, Lieberman PM Oncotarget. 2017 Jan 31;8(5):7248-7264. doi: 10.18632/oncotarget.14540. PMID:28077791[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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