West Lake University successfully analyzed the full-length structure of the new coronavirus receptor ACE2.

Recently, West Lake University Zhou Qiang Laboratory used cryoscopic mirror technology to successfully analyze the new coronavirus receptor ——— the full length structure of ACE2.
this is the first time in the world that the full-length structure of ACE2 has been resolved.
research content on February 19 at around 3 a.m. Beijing time in the pre-print platform bioRxiv launch.
this is also an important achievement of the task of emergency scientific research on the prevention and treatment of new coronavirus pneumonia in Zhejiang Province undertaken by West Lake University.
the outbreak of pneumonia caused by a new coronavirus infection, wuhan virus research institute scientists found that the new coronavirus and the 2003 SARS virus, but also through the identification of ACE2 protein into human cells, ACE2 is the "new coronavirus" invasion of the human body key.
study found that during the invasion of the human body by SARS virus and "new crown virus", ACE2 acts like a "doorknob" in which the virus catches it, opening the door to cells.
, there have been studies to analyze the three-dimensional structure of a complex formed by an extracellular domain of ACE2 and the SARS virus S protein.
recentteam team at the University of Texas at Austin recently demonstrated the S-protein structure of the new coronavirus.
However, what state does ACE2 exist in the cell membrane? What are the similarities and differences between the combination of SARS virus and ACE2? Obtaining the full-length protein of ACE2 and its compound structure with S protein will greatly help to answer these questions.
Zhou Qiang's laboratory has cracked down on this problem.
the first step, they want to obtain THE ACE2 protein full-length protein, but ace2 itself as a membrane protein is difficult to obtain in vitro stability.
Zhou Qiang and postdoctoral researcher Yu Renhong found in the literature that ACE2 and an amino acid transporter protein in the intestines B0AT1 can form a complex.
based on their past research experience, the complex is likely to stabilize ACE2.
sure, they obtained ace2 and B0AT1 high-quality and stable compounds through co-expression, and successfully parsed their three-dimensional structure with a resolution of 2.9 e, with an extracellular domain resolution of 2.7 e, which is critical for virus identification.
the comparison of the ACE2-B0AT1 complex with the previous analytical complex (the S protein of SARS-CoV and the compound of the PD domain of ACE2), the two compounds are anchored together by the PD domain.
by analyzing the full-length protein structure of ACE2, Zhou Qiang's laboratory found that ACE2 exists in the form of a dipolymer, with both accreal changes, but both conformations contain a mutually recognized interface with coronavirus.
this study provides the basis for further analysis of the three-dimensional structure of the S protein complex of full-length ACE2 and the new coronavirus.
and the work itself provides a lot of interesting clues to understanding the new coronavirus infects cells.
for example, can ace2's dipolymer and the tripolymer of the neo-coronavirus S protein be cross-linked at a higher level to promote the fusion or inward swallowing of the virus and host cell membranes? Previous studies have shown that ACE2's extracellular region, if cut, will more effectively promote the infection of the coronavirus, but the compound structure of ACE2 and B0AT1 shows that the presence of B0AT1 may prevent the protease from approaching this cutting site, does this explain that the symptoms of virus infection mainly occur in the lungs without B0AT1? This series of structural research reveals the problems to be explored in the future multidisciplinary.
"In general, the analysis of the full-length structure of ACE2 will help to understand the structural basis and functional characteristics of coronaviruses entering target cells and will play an important role in the detection and optimization of inhibitors that block entry into cells," said Professor Zhang Linxuan, director of the Center for Global Health and Infectious Diseases Research at Tsinghua University.
the first author of this article is Yan Renhong, a postdoctoral fellow at the School of Life Sciences of West Lake University, and Zhou Qiang, a researcher at the School of Life Sciences of West Lake University.
the first unit and communication unit are the key laboratory of structural biology research in Zhejiang Province of West Lake University.
work has been supported by West lake university's cryoscopic electromirror platform and supercomputing center.
what is "structural biology"? The so-called "seeing is real", structural biology will form our body, support our life activities of the biological macromolecules (proteins, nucleic acids) from a structural perspective to reveal, to understand how they work, and how their abnormality causes lesions.
research in this field can not only solve a series of major basic scientific problems in the field of life, but also help scientists to design drugs according to the specific structure of disease-related molecules, and continuously improve the quality of human life.
2019, Zhejiang Province structural biology research key laboratory was approved, Shi Igong as the laboratory director.
about receptors: Receptors are any biomolecular that binds to hormones, neurotransmitters, drugs, or intracellular signaling molecules and can cause changes in cellular function.
are divided into cell surface receptors and intracellular receptors according to the position of the receptor in the cell.
receptor itself contains at least two active sites: one is the active site that identifies and binds to the ligand, and the other is the functional active site responsible for producing the response reaction, which can only produce an response reaction after binding to the ligand to form a binary complex and changing the structure, thus initiating a series of biochemical reactions, which ultimately lead to biological effects of the target cells.
1. Most ligand signaling molecules of cell membrane receptors are hydrophilic biomacromolecules, such as cytokines, protein peptide hormones, water-soluble hormones, prostaglandins, hydropholise neurotransmitters, etc., because they cannot penetrate the target cell membrane into the cell, therefore, the receptors of such ligand signal molecules are located on the target cell membrane.
2. The receptors of most ligand signaling molecules in the cell are on the surface of the target cell because the signaling molecules are hydrophilic and cannot pass through the cell membrane.
but there are some ligand signaling molecules that can directly pass through the target cell membrane, interact with cytoplasm or cytonuclear receptors, by regulating the transcription of specific genes, using the expression of gene expression products to raise or lower, thus initiating a series of biochemical reactions, which ultimately lead to biological effects of the target cells.
these signaling molecules include fat-soluble sterol hormones, thyroid hormones and remetric acid, and gas nitric oxide.
Source: Hangzhou.com.