The Sars-CoV-2 coronavirus uses protein spikes on its surface to bind to specific receptors on the surface of human cells. This enables the virus to infect the cells. These spike structures are central to the development of vaccines because they trigger an immune response in humans.
Scientists from the Max-Planck-Institut, the Paul Ehrlich Institute, the Goethe University of Frankfurt, (all based in Germany), and the European Molecular Biology Laboratory (EMBL based throughout Europe), have analyzed these spikes protein in their natural environment. In doing so, they were able to gain some surprising insights, including discovering the unexpected flexibility of the protein spikes.
Using state-of-the-art electron microscopy at EMBL, 266 cryotomograms of about 1000 distinct viruses were generated, each featuring an average of 40 spikes on their respective surfaces.
Promising outcome for vaccine development
This is a promising outcome for the development of a vaccine, according to the researchers. “Under natural conditions, the upper spherical or V-shaped part of the spike has a structure that is readily reproduced by recombinant proteins. These proteins are used in the development of a vaccine. However, the findings concerning the stem that binds the spherical part of the spike protein to the virus surface were new,” says Martin Beck, team leader at EMBL and director of the Max Planck Institute of Biophysics.
Stem of the protein spike turns out to be flexible
“We assumed that the stem would be quite stiff. But our models as well as the images show that it is extremely flexible,” Gerhard Hummer of the Max Planck Institute for Biophysics and the University of Frankfurt explains. In the images, it rarely stood straight on the membrane but seemed to rotate in various directions. The team identified four different domains in the stem, which they named the “hip”, “knee”, “ankle” and “foot.” By combining simulations of molecular dynamics and cryotomography, they demonstrated that these domains are capable of bending.
Balloon on a string
The data shows that the spherical part of the protein spike is connected to a flexible stem. “The spike seems to move on the surface of the virus a bit like a balloon on a string.”
“This means it is able to search for the receptor so it can dock onto the target cell,” said Jacomine Krijnse Locker from the Paul Ehrlich Institute. Analyses ultimately showed that the stem is equipped with numerous glycan chains. These glycan chains could also provide the stem with some sort of protective layer of carbohydrates, disguising it so it can neutralize antibodies. According to the researchers, this is another important discovery on the road to finding effective vaccines and medicines.