The novel Coronavirus Uses its “spike protein” to invade and invade human cells. But to do so, according to a new study, spikes take shape in at least 10 different shapes.
At the beginning of Universal epidemic, Scientists rapidly identified the structure of Spike protein, Paves the way for targeting it with vaccines and other drugs. But still a lot of scientists are not aware of the interaction between the spike protein and the “dockernob” on the outer part of human cells – called the ACE2 protein. For example, they are not sure what intermediate steps the protein takes to kickstart the process of fusing, and then opening the cell, ultimately dumping viral material into the cell.
“The spike is the focal point of so much research on protein minutes,” said Donald Benton, co-lead author of the Postdoctoral Research Fellow at the Structural Biology of Disease Process Laboratory at the Francis Crick Institute in the United Kingdom. Understanding how it functions “is very important because it is the goal of most vaccination efforts as well as a lot of clinical work.”
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To understand the process of infection, Benton and his team mixed human ACE2 protein with the spike protein in the lab. Benton told Live Science that he used a very cold liquid ethane to rapidly freeze proteins, causing them to “suspend in a particular form of ice”. They then placed these samples under a cryo-electron microscope and obtained thousands of high-resolution images of frozen spike proteins at various stages of binding to ACE2 receptors.
They found that the spike protein changes shape as it binds to the ACE2 receptor. After the spike protein binds first, its structure becomes more open to allow for more bonding (imagine how easy it would be to hug someone if they opened their arms). According to a statement, the spike protein eventually binds ACE2 at all three of its binding sites, this being the “central core”. This final structure likely allows the virus cell membrane to fuse.
“This is a very complex receptor binding process compared to most virus spike proteins,” Benton said. “Flu And HIV There is a more simple activation process. “Coronovirus is involved in spike proteins, and it is possible that only a small fraction of them undergo these circulation changes, bind to human cells and infect them, Benton said.
“We know that Spike can adopt all these states we were talking about,” said co-lead author Antoine Wrobel, who is also a postdoctoral research fellow at the Francis Crick Institute’s Structural Biology of Disease Process Laboratory . “But whether each spike adopts all we can’t say is because we can only see snapshots of the type.”
Spike is too quick to change proteins. In the lab, the spike can take shape in all of these different simulations in less than 60 seconds, Wrobel told Live Science. “It would be very different in a real infection. Everything would slow down because the receptor would get stuck on the surface of a cell, so you would have to allow time for the virus to spread to this receptor,” Benton said.
Why does a spike protein undergo this many morphological changes to infect a cell? This may be “a method of virus that protects itself from recognition.” Antibodies, “Benton said. When the spike protein is in its closed states, it hides the site that binds with the receptor, maybe to avoid antibodies coming to that site and binding instead, they said.
“,” It’s very difficult to know, “Froebel said. In any case, this research reveals more surfaces on the spike proteins that are exposed during infection – as different shapes have once revealed hidden surfaces Has revealed. Researchers can then potentially develop vaccines to target these surfaces. “So we can start thinking of therapeutics that would fit only on the surface of the receptor or somewhere in the spike that would then form drugs , “Wrobel told Live Science.
Wrobel and Benton hope to find out why the coronovirus undergoes so many morphological changes, how it compares to other coronaviruses, and if these changes can help explain why this new virus spreads so easily .
The findings were published 17 September in the journal Nature.
Originally published on Live Science.