2020 Vol. 11, No. 5

High resolution structures of Herpesvirus capsid assemblyintermediate, mature capsid and virion-capsid reveal adetailed, evidence-based dynamic process for a further stagein herpesvirus assembly and maturation, addressing thepuzzle of dsDNA viruses efficient morphogenesis.
Richang Cao: pioneer advocate of dialectical materialism applied to psychological research
Baoyuan Zhang
2020, 11(5): 309-310. doi: 10.1007/s13238-019-0615-2
High resolution structure of hexameric herpesvirus DNA-packaging motor elucidates revolving mechanism and ends 20-year fervent debate
Peixuan Guo
2020, 11(5): 311-315. doi: 10.1007/s13238-020-00714-w
Progress towards revealing the mechanism of herpesvirus capsid maturation and genome packaging
Zhihai Li, Xuekui Yu
2020, 11(5): 316-317. doi: 10.1007/s13238-020-00716-8
Research journey of respirasome
Meng Wu, Jinke Gu, Shuai Zong, Runyu Guo, Tianya Liu, Maojun Yang
2020, 11(5): 318-338. doi: 10.1007/s13238-019-00681-x
Respirasome, as a vital part of the oxidative phosphorylation system, undertakes the task of transferring electrons from the electron donors to oxygen and produces a proton concentration gradient across the inner mitochondrial membrane through the coupled translocation of protons. Copious research has been carried out on this lynchpin of respiration. From the discovery of individual respiratory complexes to the report of the high-resolution structure of mammalian respiratory supercomplex I1III2IV1, scientists have gradually uncovered the mysterious veil of the electron transport chain (ETC). With the discovery of the mammalian respiratory mega complex I2III2IV2, a new perspective emerges in the research field of the ETC. Behind these advances glitters the light of the revolution in both theory and technology. Here, we give a short review about how scientists ‘see’ the structure and the mechanism of respirasome from the macroscopic scale to the atomic scale during the past decades.
Research articles
Architecture of the herpesvirus genomepackaging complex and implications for DNA translocation
Yunxiang Yang, Pan Yang, Nan Wang, Zhonghao Chen, Dan Su, Z. Hong Zhou, Zihe Rao, Xiangxi Wang
2020, 11(5): 339-351. doi: 10.1007/s13238-020-00710-0
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.
CAS9 is a genome mutator by directly disrupting DNA-PK dependent DNA repair pathway
Shuxiang Xu, Jinchul Kim, Qingshuang Tang, Qu Chen, Jingfeng Liu, Yang Xu, Xuemei Fu
2020, 11(5): 352-365. doi: 10.1007/s13238-020-00699-6
With its high efficiency for site-specific genome editing and easy manipulation, the clustered regularly interspaced short palindromic repeats (CRISPR)/ CRISPR associated protein 9 (CAS9) system has become the most widely used gene editing technology in biomedical research. In addition, significant progress has been made for the clinical development of CRISPR/CAS9 based gene therapies of human diseases, several of which are entering clinical trials. Here we report that CAS9 protein can function as a genome mutator independent of any exogenous guide RNA (gRNA) in human cells, promoting genomic DNA double-stranded break (DSB) damage and genomic instability. CAS9 interacts with the KU86 subunit of the DNA-dependent protein kinase (DNA-PK) complex and disrupts the interaction between KU86 and its kinase subunit, leading to defective DNA-PK-dependent repair of DNA DSB damage via non-homologous end-joining (NHEJ) pathway. XCAS9 is a CAS9 variant with potentially higher fidelity and broader compatibility, and dCAS9 is a CAS9 variant without nuclease activity. We show that XCAS9 and dCAS9 also interact with KU86 and disrupt DNA DSB repair. Considering the critical roles of DNA-PK in maintaining genomic stability and the pleiotropic impact of DNA DSB damage responses on cellular proliferation and survival, our findings caution the interpretation of data involving CRISPR/CAS9-based gene editing and raise serious safety concerns of CRISPR/CAS9 system in clinical application.
Structures of the portal vertex reveal essential protein-protein interactions for Herpesvirus assembly and maturation
Nan Wang, Wenyuan Chen, Ling Zhu, Dongjie Zhu, Rui Feng, Jialing Wang, Bin Zhu, Xinzheng Zhang, Xiaoqing Chen, Xianjie Liu, Runbin Yan, Dongyao Ni, Grace Guoying Zhou, Hongrong Liu, Zihe Rao, Xiangxi Wang
2020, 11(5): 366-373. doi: 10.1007/s13238-020-00711-z
Structural changes of a bacteriophage upon DNA packaging and maturation
Wenyuan Chen, Hao Xiao, Xurong Wang, Shuanglin Song, Zhen Han, Xiaowu Li, Fan Yang, Li Wang, Jingdong Song, Hongrong Liu, Lingpeng Cheng
2020, 11(5): 374-379. doi: 10.1007/s13238-020-00715-9
TCF-1 deficiency influences the composition of intestinal microbiota and enhances susceptibility to colonic inflammation
Guotao Yu, Fang Wang, Menghao You, Tiansong Xu, Chunlei Shao, Yuning Liu, Ruiqi Liu, Min Deng, Zhihong Qi, Zhao Wang, Jingjing Liu, Yingpeng Yao, Jingjing Chen, Zhen Sun, Shanshan Hao, Wenhui Guo, Tianyan Zhao, Zhengquan Yu, Qian Zhang, Yaofeng Zhao, Feng Chen, Shuyang Yu
2020, 11(5): 380-386. doi: 10.1007/s13238-020-00689-8