5WMF

Crystal structure of the Hexameric Ring of Epstein-Barr Virus Nuclear Antigen-1, EBNA1

5WMF の概要

• エントリーDOI: 10.2210/pdb5wmf/pdb
• 分子名称: Epstein-Barr nuclear antigen 1 (2 entities in total)
• 機能のキーワード: ebna1, dna binding protein, epstein-barr virus, viral protein
• 由来する生物種: Epstein-Barr virus (HHV-4)
• 細胞内の位置: Host nucleus : P03211
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 99709.13

構造登録者

Messick, T.E. (登録日: 2017-07-28, 公開日: 2017-08-09, 最終更新日: 2023-10-04)

主引用文献

Deakyne, J.S.,Malecka, K.A.,Messick, T.E.,Lieberman, P.M.
Structural and Functional Basis for an EBNA1 Hexameric Ring in Epstein-Barr Virus Episome Maintenance.
J. Virol., 91:-, 2017

PubMed Abstract: Epstein-Barr virus (EBV) establishes a stable latent infection that can persist for the life of the host. EBNA1 is required for the replication, maintenance, and segregation of the latent episome, but the structural features of EBNA1 that confer each of these functions are not completely understood. Here, we have solved the X-ray crystal structure of an EBNA1 DNA-binding domain (DBD) and discovered a novel hexameric ring oligomeric form. The oligomeric interface pivoted around residue T585 as a joint that links and stabilizes higher-order EBNA1 complexes. Substitution mutations around the interface destabilized higher-order complex formation and altered the cooperative DNA-binding properties of EBNA1. Mutations had both positive and negative effects on EBNA1-dependent DNA replication and episome maintenance with OriP. We found that one naturally occurring polymorphism in the oligomer interface (T585P) had greater cooperative DNA binding , minor defects in DNA replication, and pronounced defects in episome maintenance. The T585P mutant was compromised for binding to OriP as well as for assembling the origin recognition complex subunit 2 (ORC2) and trimethylated histone 3 lysine 4 (H3K4me3) at OriP. The T585P mutant was also compromised for forming stable subnuclear foci in living cells. These findings reveal a novel oligomeric structure of EBNA1 with an interface subject to naturally occurring polymorphisms that modulate EBNA1 functional properties. We propose that EBNA1 dimers can assemble into higher-order oligomeric structures important for diverse functions of EBNA1. Epstein-Barr virus is a human gammaherpesvirus that is causally associated with various cancers. Carcinogenic properties are linked to the ability of the virus to persist in the latent form for the lifetime of the host. EBNA1 is a sequence-specific DNA-binding protein that is consistently expressed in EBV tumors and is the only viral protein required to maintain the viral episome during latency. The structural and biochemical mechanisms by which EBNA1 allows the long-term persistence of the EBV genome are currently unclear. Here, we have solved the crystal structure of an EBNA1 hexameric ring and characterized key residues in the interface required for higher-order complex formation and long-term plasmid maintenance.

PubMed: 28701406
DOI: 10.1128/JVI.01046-17

実験手法

X-RAY DIFFRACTION (1.9 Å)