The spike protein on the surface of the SARS-CoV-2 coronavirus can adopt at least ten distinct structural states, when in contact with the human virus receptor ACE2, according to research from the Francis Crick Institute published in Nature.
The infection begins when a spike protein binds with ACE2 cell surface receptors and, at later stages, catalyzes the release of the virus genome into the cell. However, the exact nature of the ACE2 binding to the SARS-CoV-2 spike remains unknown.
The team incubated a mixture of spike protein and ACE2 before trapping different forms of the protein by rapid freezing in liquid ethane. They examined these samples using cryo-electron microscopy, obtaining tens of thousands of high-resolution images of the different binding stages.
They observed that the spike protein exists as a mixture of closed and open structures., Following ACE2 binding at a single open site, the spike protein becomes more open, leading to a series of favorable conformational changes, priming it for additional binding. Once the spike is bound to ACE2 at all three of its binding sites, its central core becomes exposed, which may help the virus to fuse to the cell membrane, permitting infection.
"We can see that as the spike becomes more open, the stability of the protein will reduce, which may increase the ability of the protein to carry out membrane fusion, allowing infection."
reference
Receptor binding and priming of the spike protein of SARS-CoV-2 for membrane fusion. Nature (2020). doi.org/10.1038/s41586-020-2772-0