8OJD

HSV-1 DNA polymerase beta-hairpin loop

8OJD の概要

• エントリーDOI: 10.2210/pdb8ojd/pdb
• 関連するPDBエントリー: 8OJ6
• EMDBエントリー: 16906 16912
• 分子名称: DNA polymerase catalytic subunit, DNA (47-MER), DNA (68-MER), ... (4 entities in total)
• 機能のキーワード: dna, polymerase, complex, transferase
• 由来する生物種: Human alphaherpesvirus 1 strain KOS; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 172215.65

構造登録者

Gustavsson, E.,Grunewald, K.,Elias, P.,Hallberg, B.M. (登録日: 2023-03-24, 公開日: 2024-04-03, 最終更新日: 2024-07-17)

主引用文献

Gustavsson, E.,Grunewald, K.,Elias, P.,Hallberg, B.M.
Dynamics of the Herpes simplex virus DNA polymerase holoenzyme during DNA synthesis and proof-reading revealed by Cryo-EM.
Nucleic Acids Res., 52:7292-7304, 2024

PubMed Abstract: Herpes simplex virus 1 (HSV-1), a double-stranded DNA virus, replicates using seven essential proteins encoded by its genome. Among these, the UL30 DNA polymerase, complexed with the UL42 processivity factor, orchestrates leading and lagging strand replication of the 152 kb viral genome. UL30 polymerase is a prime target for antiviral therapy, and resistance to current drugs can arise in immunocompromised individuals. Using electron cryo-microscopy (cryo-EM), we unveil the dynamic changes of the UL30/UL42 complex with DNA in three distinct states. First, a pre-translocation state with an open fingers domain ready for nucleotide incorporation. Second, a halted elongation state where the fingers close, trapping dATP in the dNTP pocket. Third, a DNA-editing state involving significant conformational changes to allow DNA realignment for exonuclease activity. Additionally, the flexible UL30 C-terminal domain interacts with UL42, forming an extended positively charged surface binding to DNA, thereby enhancing processive synthesis. These findings highlight substantial structural shifts in the polymerase and its DNA interactions during replication, offering insights for future antiviral drug development.

PubMed: 38806233
DOI: 10.1093/nar/gkae374

実験手法

ELECTRON MICROSCOPY (2.46 Å)