Flexible and protected
New findings on SARS-CoV-2 protein shed light on virus's ability to
infect cells

Date:
August 18, 2020
Source:
European Molecular Biology Laboratory
Summary:
Coronavirus researchers have focused on the surface structure of
SARS- CoV-2 to gain insights they can use for the development of
vaccines and effective therapeutics to treat infected patients.



FULL STORY ==========================================================================
In the fight against the coronavirus, SARS-CoV-2 researchers from multiple research institutions in Germany have combined their resources to study
the spike protein on the surface of the virus. With its spikes, the virus
binds to human cells and infects them. The study gave surprising insights
into the spike protein, including an unexpected freedom of movement and
a protective coat to hide it from antibodies. The results are published
in Science.


==========================================================================
At the start of a COVID-19 infection, the coronavirus SARS-CoV-2 docks
onto human cells using the spike-like proteins on its surface. The spike protein is at the centre of vaccine development because it triggers
an immune response in humans. A group of German scientists, including
members of the European Molecular Biology Laboratory (EMBL) in Heidelberg,
the Max Planck Institute of Biophysics, the Paul-Ehrlich-Institut, and
Goethe University Frankfurt have focused on the surface structure of the
virus to gain insights they can use for the development of vaccines and
of effective therapeutics to treat infected patients.

The team combined cryo-electron tomography, subtomogram averaging,
and molecular dynamics simulations to analyse the molecular structure
of the spike protein in its natural environment, on intact virions, and
with near-atomic resolution. Using EMBL's state-of-the-art cryo-electron microscopy imaging facility, 266 cryotomograms of about 1000 different
viruses were generated, each carrying an average of 40 spikes on its
surface. Subtomogram averaging and image processing, combined with
molecular dynamics simulations, finally provided the important and novel structural information on these spikes.

The results were surprising: the data showed that the globular portion
of the spike protein, which contains the receptor-binding region and
the machinery required for fusion with the target cell, is connected to
a flexible stalk.

"The upper spherical part of the spike has a structure that is well
reproduced by recombinant proteins used for vaccine development,"
explains Martin Beck, EMBL group leader and a director of the Max Planck Institute (MPI) of Biophysics. "However, our findings about the stalk,
which fixes the globular part of the spike protein to the virus surface,
were new." "The stalk was expected to be quite rigid," adds Gerhard
Hummer, from the MPI of Biophysics and the Institute of Biophysics at
Goethe University Frankfurt.

"But in our computer models and in the actual images, we discovered
that the stalks are extremely flexible." By combining molecular dynamics simulations and cryo-electron tomography, the team identified the three
joints -- hip, knee and ankle -- that give the stalk its flexibility.

"Like a balloon on a string, the spikes appear to move on the surface
of the virus and thus are able to search for the receptor for docking to
the target cell," explains Jacomine Krijnse Locker, group leader at the Paul-Ehrlich- Institut. To prevent infection, these spikes are targeted
by antibodies.

However, the images and models also showed that the entire spike protein, including the stalk, is covered with chains of glycans -- sugar-like
molecules.

These chains provide a kind of protective coat that hides the spikes
from neutralising antibodies: another important finding on the way to
effective vaccines and medicines.


========================================================================== Story Source: Materials provided by
European_Molecular_Biology_Laboratory. Note: Content may be edited for
style and length.


========================================================================== Journal Reference:
1. Beata Turoňova', Mateusz Sikora, Christoph Schu"rmann, Wim
J. H.

Hagen, Sonja Welsch, Florian E. C. Blanc, So"ren von Bu"low, Michael
Gecht, Katrin Bagola, Cindy Ho"rner, Ger van Zandbergen, Jonathan
Landry, Nayara Trevisan Doimo de Azevedo, Shyamal Mosalaganti,
Andre Schwarz, Roberto Covino, Michael D. Mu"hlebach, Gerhard
Hummer, Jacomine Krijnse Locker, Martin Beck. In situ structural
analysis of SARS-CoV-2 spike reveals flexibility mediated by three
hinges. Science, Aug. 18, 2020; DOI: 10.1126/science.abd5223 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/08/200818103838.htm

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