Structure of monkeypox virus DNA polymerase holoenzyme

• 成果类型: Article
• 署名作者: Peng, Qi; Xie, Yufeng; Kuai, Lu; Wang, Han; Qi, Jianxun; Gao, George F.; Shi, Yi
• 署名单位: Chinese Academy of Sciences; Institute of Microbiology, CAS; Tsinghua University; Peking University; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS; Chinese Academy of Sciences; Chinese Academy of Medical Sciences - Peking Union Medical College
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8646
• DOI: 10.1126/science.ade6360
• 发表日期: 2023-01-06
• 页码: 100-105
• 关键词: hiv-1 reverse-transcriptase; processivity factor; crystal-structure; vaccinia dna; glycosylase; a20; replication; virulence; complex; ligase

摘要

The World Health Organization declared mpox (or monkeypox) a public health emergency of international concern in July 2022, and prophylactic and therapeutic measures are in urgent need. The monkeypox virus (MPXV) has its own DNA polymerase F8, together with the processive cofactors A22 and E4, constituting the polymerase holoenzyme for genome replication. Here, we determined the holoenzyme structure in complex with DNA using cryo-electron microscopy at the global resolution of similar to 2.8 angstroms. The holoenzyme possesses an architecture that suggests a forward sliding clamp processivity mechanism for viral DNA replication. MPXV polymerase has a DNA binding mode similar to that of other B-family DNA polymerases from different species. These findings reveal the mechanism of the MPXV genome replication and may guide the development of anti-poxvirus drugs.