Architecture of the herpesvirus genomepackaging complex and implications for DNA translocation

doi:10.1007/s13238-020-00710-0

Protein Cell

2020, Vol. 11

Issue (5) : 339-351 https://doi.org/10.1007/s13238-020-00710-0

RESEARCH ARTICLE

Architecture of the herpesvirus genomepackaging complex and implications for DNA translocation

Yunxiang Yang^1,², Pan Yang¹, Nan Wang¹, Zhonghao Chen¹, Dan Su², Z. Hong Zhou³, Zihe Rao^1,^4,⁵(

), Xiangxi Wang¹(

)

¹. CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
². State Key Laboratory of Biotherapy, West China Hospital, Collaborative Innovation Center for Biotherapy, Sichuan University, Chengdu 610041, China
³. Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA
⁴. Laboratory of Structural Biology, School of Medicine, Tsinghua University, Beijing 100084, China
⁵. State Key Laboratory of Medicinal Chemical Biology and College of Life Science, Nankai University, Tianjin 300353, China

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Abstract

Genome packaging is a fundamental process in a viral life cycle and a prime target of antiviral drugs. Herpesviruses use an ATP-driven packaging motor/terminase complex to translocate and cleave concatemeric dsDNA into procapsids but its molecular architecture and mechanism are unknown. We report atomic structures of a herpesvirus hexameric terminase complex in both the apo and ADP•BeF3-bound states. Each subunit of the hexameric ring comprises three components—the ATPase/terminase pUL15 and two regulator/fixer proteins, pUL28 and pUL33—unlike bacteriophage terminases. Distal to the nuclease domains, six ATPase domains form a central channel with conserved basicpatches conducive to DNA binding and trans-acting arginine fingers are essential to ATP hydrolysis and sequential DNA translocation. Rearrangement of the nuclease domains mediated by regulatory domains converts DNA translocation mode to cleavage mode. Our structures favor a sequential revolution model for DNA translocation and suggest mechanisms for concerted domain rearrangements leading to DNA cleavage.

Keywords dsDNA virus genome packaging viral maturation terminase complex drug target

Corresponding Author(s): Zihe Rao,Xiangxi Wang

Issue Date: 02 June 2020

Cite this article:

Yunxiang Yang,Pan Yang,Nan Wang, et al. Architecture of the herpesvirus genomepackaging complex and implications for DNA translocation[J]. Protein Cell, 2020, 11(5): 339-351.

URL:

https://academic.hep.com.cn/pac/EN/10.1007/s13238-020-00710-0
https://academic.hep.com.cn/pac/EN/Y2020/V11/I5/339

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Yang Wu, Zhiyong Lou, Yi Miao, Yue Yu, Hui Dong, Wei Peng, Mark Bartlam, Xuemei Li, Zihe Rao. Structures of EV71 RNA-dependent RNA polymerase in complex with substrate and analogue provide a drug target against the hand-foot-and-mouth disease pandemic in China[J]. Prot Cell, 2010, 1(5): 491-500.

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