Pan Yang
Nan Wang
Zhonghao Chen
Dan Su
Z. Hong Zhou
Zihe Rao
Xiangxi Wang
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
Funds: We thank Xiaojun Huang, Boling Zhu, Tongxin Niu and Deyin Fan for cryo-EM technical supports. The cryo-EM data sets were collected at Center for Biological imaging (CBI), Institute of Biophysics. Work was supported by the Strategic Priority Research Program (XDB29010000), the Key Programs of the Chinese Academy (KJZDSW-L05), National Key Research and Development Program (2018YFA0900801 and 2017YFC0840300) and National Science Foundation of China (31800145 and 81520108019). Xiangxi Wang was supported by Ten Thousand Talent Program and the NSFS Innovative Research Group (No. 81921005).
Received Date: 2020-02-25
Rev Recd Date:2020-03-12
Abstract
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
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