Architecture of the herpesvirus genome-packaging complex and implications for DNA translocation.
10.1007/s13238-020-00710-0
- Author:
Yunxiang YANG
1
;
Pan YANG
1
;
Nan WANG
1
;
Zhonghao CHEN
1
;
Dan SU
2
;
Z Hong ZHOU
3
;
Zihe RAO
4
;
Xiangxi WANG
5
Author Information
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. CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China. raozh@tsinghua.edu.cn.
5. CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China. xiangxi@ibp.ac.cn.
- Publication Type:Journal Article
- Keywords:
drug target;
dsDNA virus;
genome packaging;
terminase complex;
viral maturation
- From:
Protein & Cell
2020;11(5):339-351
- CountryChina
- Language:English
-
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 basic-patches 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.
