4E2I

The Complex Structure of the SV40 Helicase Large T Antigen and p68 Subunit of DNA Polymerase Alpha-Primase

4E2I の概要

• エントリーDOI: 10.2210/pdb4e2i/pdb
• 分子名称: Large T antigen, DNA polymerase alpha subunit B, ZINC ION (3 entities in total)
• 機能のキーワード: replication initiation, hydrolase-dna binding complex, hydrolase-dna binding protein complex, hydrolase/dna binding protein
• 由来する生物種: Simian virus 40 (SV40); 詳細
• 細胞内の位置: Nucleus: Q14181
• タンパク質・核酸の鎖数: 23
• 化学式量合計: 598246.55

構造登録者

Zhou, B.,Arnett, D.R.,Yu, X.,Brewster, A.,Sowd, G.A.,Xie, C.L.,Vila, S.,Gai, D.,Fanning, E.,Chen, X.S. (登録日: 2012-03-08, 公開日: 2012-06-13, 最終更新日: 2024-02-28)

主引用文献

Zhou, B.,Arnett, D.R.,Yu, X.,Brewster, A.,Sowd, G.A.,Xie, C.L.,Vila, S.,Gai, D.,Fanning, E.,Chen, X.S.
Structural basis for the interaction of a hexameric replicative helicase with the regulatory subunit of human DNA polymerase alpha-primase.
J.Biol.Chem., 287:26854-26866, 2012

PubMed Abstract: DNA polymerase α-primase (Pol-prim) plays an essential role in eukaryotic DNA replication, initiating synthesis of the leading strand and of each Okazaki fragment on the lagging strand. Pol-prim is composed of a primase heterodimer that synthesizes an RNA primer, a DNA polymerase subunit that extends the primer, and a regulatory B-subunit (p68) without apparent enzymatic activity. Pol-prim is thought to interact with eukaryotic replicative helicases, forming a dynamic multiprotein assembly that displays primosome activity. At least three subunits of Pol-prim interact physically with the hexameric replicative helicase SV40 large T antigen, constituting a simple primosome that is active in vitro. However, structural understanding of these interactions and their role in viral chromatin replication in vivo remains incomplete. Here, we report the detailed large T antigen-p68 interface, as revealed in a co-crystal structure and validated by site-directed mutagenesis, and we demonstrate its functional importance in activating the SV40 primosome in cell-free reactions with purified Pol-prim, as well as in monkey cells in vivo.

PubMed: 22700977
DOI: 10.1074/jbc.M112.363655

実験手法

X-RAY DIFFRACTION (5 Å)