On March 27, an academic paper from the Chinese research team appeared on the cover of the world famous academic journal Science.
The novel coronavirus is the result of this research. Novel coronavirus novel coronavirus (COVID-19) has been successfully analyzed for the full-length three-dimensional structure of the receptor ACE2 of the novel coronavirus (COVID-19), and the three-dimensional structure of the novel S protein receptor binding domain of the coronavirus and the full-length protein complex of the cell surface receptor.
And it is worth mentioning that this paper is the first cover paper published in Science》 magazine since the global outbreak devoted to new crown viruses.
S protein and ACE2: the key of new coronavirus invading cells
The new coronavirus-induced pneumonia has brought coronavirus, S protein, ACE2 and these obscure biological terms into public view again.
Researchers have found that the key to new coronavirus infections in human cells is the binding of coronavirus S proteins to human ACE2 proteins. Exactly, the S protein of the virus
So, what is s protein?
S protein is called Spike Glycoprotein (prickly glycoprotein). It's in the outermost layer of the new crown virus, like a bulge
According to a new analysis by the team at the University of Texas at Austin, the new coronavirus S protein exists in the form of a trimer, with more than 1300 amino acids in each monomer, more than 300 of which form
So, what is ACE2?
ACE2,Angiotensin-converting enzyme 2, Chinese full name is angiotensin converting enzyme 2, a protein involved in blood pressure regulation in the human body, widely found in the lung, heart, kidney and intestine.
So, how can a protein of human cell contact with virus?
Tao Liang, a special researcher of West Lake University, uses an image metaphor:
If you think of the human body as a house and the new crown virus as a robber, then ACE2 is the house
Therefore, the study of S protein and ACE2 is the key to understand the process of new coronavirus invading cells, which is also the research focus of Zhou Qiang Laboratory of West Lake University.
At the same time, as the University of California, Los Angeles, molecular and medical pharmacology, bioengineering special professor Sun Ren said:
The interaction between S protein and its receptor is one of the important determinants of virus transmission. Therefore, it is an effective way for us to understand the transmission mechanism and predict the transmission ability by observing the sequence and corresponding structure of S protein receptor binding domain in the process of virus cross species transmission and after transmission.
S protein is like a bridge across the surface of ACE2
The results of this paper on the cover of the Science》 are essentially an explanation of the whole picture of viruses S proteins and ACE2 and their interaction with each other. The title of the paper is:
Structural basis for the recognition of the SARS-CoV-2 by full-length human ACE2
Based on the analysis of the high-resolution three-dimensional spatial structure of ACE2 full-length protein, this paper analyzes the complex structure of ACE2 full-length protein and new coronavirus s protein receptor binding domain, with an overall resolution of 2.9 angstroms Anders Jonas ngstrm), in which the resolution of S protein receptor binding domain is 3.5 angstroms.
So, what did the researchers see from the structure of the parsed complex?
It turns out that in morphology, the S protein of the new coronavirus is like a bridge across the surface of ACE2, like a hand of the virus, holding on to ACE2 tightly, which is similar to SARS virus. The receptor binding domain of S protein of new coronavirus is very similar to that of SARS virus, and the similarity is 82%.
Further analysis, the researchers can see which amino acids interact with ACE2 on the surface of the new coronavirus. It can be seen that compared with the interaction between SARS virus and ACE2, some amino acid residues of S protein of new coronavirus have changed greatly.
This may explain why the binding ability of SARS and ACE2 is different, which may affect the infectivity of the virus.
However, whether the virus is more or less contagious needs to be tested by other experiments.
As early as February 21, Beijing time, the results of this study were published bioRxiv the pre-printing platform and made public to the whole society at the first time
Finally, it appeared on the cover of science on March 27.
It is worth mentioning that the research team of Professor Wang Xinquan of Tsinghua University and Qi Jianxun of Institute of Microbiology of Chinese Academy of Sciences independently analyzed the crystal structure of the N-terminal protease domain of ACE2 and the S-protein receptor binding domain of new coronavirus.
The information is mutually supportive and complementary to the relevant electron microscope structures obtained by Zhou Qiang team.
What exactly does this result mean?
The virus-related scientific research has attracted much attention as the new outbreak continues to spread worldwide
In this regard, Zhou Qiang's team also made specific instructions.
Zhou Qiang's team said, This analysis of the complex structure belongs to the breakthrough in the field of basic research, and the development of anti-epidemic drugs is not necessarily linked.
On the other hand, however, it is indeed very important. To a great extent, the structure of the protein determines its properties and functions, and to see clearly S proteins, ACE2 and their interacting structures of the new coronavirus is equivalent to seeing clearly
On the basis of this study, researchers of computational biology can build different models on this basis, and then carry out targeted research to determine what kind of mutation may further improve the interaction between S protein and ACE2, so as to design for s egg white or ACE2 Drugs and antibodies for proteins; or design small molecules to disrupt their interactions.
All of these can provide a solid foundation for drug design and development of detection methods.
Lei Feng net (public number: Lei Feng net) noted that the study was also recognized by experts in many disciplines. For example, Howard Hughes Research Fellow, Department of Biophysics, Southwest Medical Center, University of Texas, Michael K.Rosen believes:
The novel coronavirus pneumonia research by Zhou Qiang team has made important progress in understanding how the new crown virus infect human cells. The research results will play a key role in the diagnosis and treatment of new crown pneumonia.
Sun Ren, a distinguished professor of molecular and medical pharmacology and bioengineering at UCLA, also said:
Zhou Qiang's team's research an important step in understanding the mechanism of virus invading cells and helps us to further understand the spread of virus across species and among species. More key information may be obtained by comparing the S proteins of different coronaviruses with the ACE2, of different hosts on the interaction patterns of their multiple combinations.
The author team behind this paper
The result of this paper comes from Zhou Qiang Laboratory of West Lake University.
Among them, Zhou Qiang, a researcher of the school of life sciences of West Lake University, is the corresponding author, and Yan Renhong, a postdoctoral of the school of life sciences of West Lake University, is the first author.
Zhou Qiang, born in 1982, graduated from Tsinghua University with a master's degree, and continued to stay in the laboratory for postdoctoral research after graduation; in 2015, after leaving the station, he worked as an associate researcher in the research group of Professor Yan Ning of Tsinghua University School of medicine; in early 2019, he joined West Lake University as a West Lake scholar and specially hired researcher to carry out independent research.
In the field of research, Dr. Zhou Qiang has been engaged in the study and research of single particle technology of frozen electron microscopy for a long time. He has worked with colleagues and collaborators to analyze the structure of several important biomacromolecule complexes or membrane proteins, including snap-snare complex, inflammatory complex, Niemann pick C1 (NPC1) protein, eukaryotic voltage-gated sodium channel, etc.
Among them, the true nuclear pressure gated sodium ion channel combined with gated regulatory toxin Dc1a and the resolution of tetrodotoxin reached 2.6 E, which is the highest resolution of membrane protein structure analyzed by single particle technology of freeze electron microscope, which lays the foundation for the subsequent development of small molecule drug based on structure.
However, Zhou Qiang's doctoral research group mainly uses frozen electron microscopy as the main research method, combining with biochemistry, molecular biology, computational biology and other technologies to study the structure and working mechanism of biomacromolecule complexes and membrane proteins related to major diseases or important biological processes.
Novel coronavirus pneumonia has been studied by Lei Feng in the past two years. It has been targeting several target proteins. ACE2 is one of them. After the outbreak of the new crown pneumonia, the Zhou Qiang team rapidly raised the priority of ACE2 research, and finally obtained the research results.
Congratulations to team Zhou Qiang!