3D cell receptor structure of nCoV

For the first time, the team successfully analyzed the ACE2 receptor structure, helping to understand and find ways to limit the replication of nCoV in the body.

In the morning of February 19, postdoctoral researcher Ren Renhong and researcher Zhou Qiang of the West Lake University Laboratory in China published a successful analysis of the spatial structure of nCoV's ACE2 receptor. using cryo-EM (cryo-EM) microscopy - a method of freezing of samples used in electron microscopes that allows the freezing of biological molecules while preserving their shape. The research was published in bioRxiv, an open access repository for biological sciences at the Cold Spring Harbortory Laboratory (USA).

Structure diagram of ACE2 complex and amino acid transporter B0AT1. Photo: The Paper.

This is the first study in the world to successfully analyze the entire length of the ACE2 structure (the receptor that nCoV attaches to multiply into human body cells), an important step in the scientific research task. Covid-19 epidemic prevention and control.

According to the study, ACE2 is an enzyme receptor of SARS, also plays an important role in the relationship of nCoV with human cells. Like SARS in 2003, nCoV invades human cells by recognizing ACE2's protein. ACE2 is like a "door handle" that makes it easy for nCoV to enter the body's cells.

The team collected full lengths with the S protein in ACE2 but the receptor itself was difficult to collect in vitro. During the research, postdoctoral researcher Ren Renhong found that ACE2 and the amino acid transporter B0AT1 can form a complex.

Cryo-EM density of ACE2 complex and amino acid transporter B0AT1. Photo: The Paper.

Based on previous research experience, the team said this complex has a high ACE2 stability. Thanks to this, the group obtained a stable and highly coherent complex between ACE2 and B0AT1 and successfully performed and analyzed the 3D structure of this complex thanks to a cold electron microscope at 2.9 Angstrom resolution. (1 Angstrom = 0.1 Nanometers).

By analyzing the structure and length of the ACE2 protein, the team also found that ACE2 exists as a pair with changes in shape, but all contain external identities similar to those of nCoV.

Earlier, the University of Texas team at Austin analyzed the 3D structure of a complex formed by the extracellular domain ACE2 and the S protein in the SARS virus, thereby indicating the S protein structure in the nCoV virus. However, ACE2 receptor status on the cell membrane has not been determined yet as well as the difference of ACE2 between SARS virus and nCoV. Only the length and complex structure of S protein in ACE2 can be found to solve these problems.

Researcher Zhou Qiang (left) and postdoctoral researcher Ren Renhong (right), West Lake University, China. Photo: The Paper.

"The complete structure analysis of the ACE2 receptor helps to understand the functional characteristics of nCoV in the process of invading target cells, thereby finding and optimizing the cell entry inhibitors of nCoV, "said Professor Zhang Linqi, Director of the Center for Research on Infectious Diseases and Global Health, Tsinghua University (China).

The study also provides "clues" to understanding the infectious potential of nCoV virus cells, such as whether the ACE2 receptor-paired form and the S-bound triple form can be cross-linked. higher or not, thereby promoting fusion of nCoV with the host cell membrane. Does ACE2's extracellular site fragmentation promote nCoV infection? These issues are still being investigated by researchers at Westlake.

Postdoctoral researcher Ren Renhong, of the West Lake University, which specializes in biological science issues, is currently a member of the Biological Structure Research Laboratory of Zhejiang Province, China.

Researcher Zhou Qiang is the principal researcher at West Lake University Laboratory, specializing in cell biology, stem cell and cell therapy.