Achieve new achievements in the atomic model of viral transcripts in biophysics

On April 6, the Proceedings of the National Academy of Sciences (PNAS) published a research paper titled Cryo-EM structure of a transcribing cypovirus in collaboration with Zhu Ping and Sun Fei of the Institute of Biophysics, Chinese Academy of Sciences. In this study, the three-dimensional reconstruction method of cryo-electron microscopy was used for the first time to analyze the near-atomic resolution (4.1 Ã…) three-dimensional structure of the double-stranded RNA virus in the process of transcription, and to construct a full amino acid atomic structure model of the virus transcribed state. This is Zhu Ping, Sun Fei, Cheng Lingpeng and others in the field of double-stranded RNA virus structure and function research following the publication of Atomic model of a cypovirus built from cryo-EM structure provides insight into the mechanism of mRNA cappin research paper on PNAS last year. Another latest development.

The transcription state of the virus is metastable, and it is difficult to form regularly arranged crystals. Therefore, there is no report on the crystal structure of the transcribed virus. The three-dimensional reconstruction technique of cryo-electron microscopy is very suitable for the analysis of the structure of such biological macromolecular complexes. The structural studies of several transcribed viruses have been reported by cryo-electron microscopy. The question remains unanswered.

This study is the first to advance the structural accuracy of transcribed double-stranded RNA viruses to near-atomic resolution. It is also the only three-dimensional reconstruction of cryogenic electron microscopy of viral transcribed states that can see a single amino acid residue. This study reveals an important link in the life cycle of double-stranded RNA viruses-the conformational changes that occur in the transcription link to adapt to their transcriptional functions, not only to provide a long-term hypothesis about the release channel of double-stranded RNA viruses mRNA It has strong structural evidence, and has also observed the GTase enzyme active site of this kind of virus in the process of mRNA capping and its interaction with the reaction substrate, thus revealing the process of RNA transcription and capping The mechanism by which the structural proteins coordinate with each other allows the smooth flow of new RNA from viruses, clarifying the long-term debate on RNA release channels during the transcription of double-stranded RNA viruses. This provides a structural basis for people to further understand and understand the mechanism of viral RNA transcription and capping, and ultimately to achieve self-replication for such viruses.

The research was completed on the Titan Krios 300kV electron microscope of the Protein Science Research Platform of the Chinese Academy of Sciences. This result indicates that the Bioimaging Technology Laboratory of the Protein Science Research Platform of the Chinese Academy of Sciences is gradually maturing.

The first author of the article is Yang Chongwen, a PhD student in the Zhu Ping research group of the Institute of Biophysics, and Zhu Ping and Associate Researcher Cheng Lingpeng are co-corresponding authors. Ji Gang, Senior Engineer of the Institute of Biophysics, Zhang Kai, Ph.D. Electron microscopy imaging and atomic model construction work were carried out. Professor Liu Hongrong of Hunan Normal University participated in some research work.

The research was supported by the Ministry of Science and Technology, the National Natural Science Foundation of China and the Chinese Academy of Sciences.

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