5CYN

JC Virus large T-antigen origin binding domain F258L mutant

5CYN の概要

• エントリーDOI: 10.2210/pdb5cyn/pdb
• 分子名称: Large T antigen, 1,2-ETHANEDIOL (3 entities in total)
• 機能のキーワード: dna binding domain, origin binding domain, viral protein, dna binding protein
• 由来する生物種: JC polyomavirus (JCPyV)
• 細胞内の位置: Host nucleus : P03072
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 15054.31

構造登録者

Meinke, G.,Bohm, A.,Bullock, P.A. (登録日: 2015-07-30, 公開日: 2015-12-16, 最終更新日: 2023-09-27)

主引用文献

Meinke, G.,Phelan, P.J.,Shin, J.,Gagnon, D.,Archambault, J.,Bohm, A.,Bullock, P.A.
Structural Based Analyses of the JC Virus T-Antigen F258L Mutant Provides Evidence for DNA Dependent Conformational Changes in the C-Termini of Polyomavirus Origin Binding Domains.
Plos Pathog., 12:e1005362-e1005362, 2016

PubMed Abstract: The replication of human polyomavirus JCV, which causes Progressive Multifocal Leukoencephalopathy, is initiated by the virally encoded T-antigen (T-ag). The structure of the JC virus T-ag origin-binding domain (OBD) was recently solved by X-ray crystallography. This structure revealed that the OBD contains a C-terminal pocket, and that residues from the multifunctional A1 and B2 motifs situated on a neighboring OBD molecule dock into the pocket. Related studies established that a mutation in a pocket residue (F258L) rendered JCV T-ag unable to support JCV DNA replication. To establish why this mutation inactivated JCV T-ag, we have solved the structure of the F258L JCV T-ag OBD mutant. Based on this structure, it is concluded that the structural consequences of the F258L mutation are limited to the pocket region. Further analyses, utilizing the available polyomavirus OBD structures, indicate that the F258 region is highly dynamic and that the relative positions of F258 are governed by DNA binding. The possible functional consequences of the DNA dependent rearrangements, including promotion of OBD cycling at the replication fork, are discussed.

PubMed: 26735515
DOI: 10.1371/journal.ppat.1005362

実験手法

X-RAY DIFFRACTION (2.7 Å)