AUG 24, 2020 4:48 AM PDT

A Shield Surrounds the Flexible SARS-CoV-2 Spike Protein

WRITTEN BY: Carmen Leitch

Researchers know that the viruses including SARS-CoV-2 have a spike protein that allows them to bind to receptors on host cells. In the case of SARS-CoV-2, ACE2 receptors are among those that can bind to the SARS-CoV-2 spike protein, which allows the virus to bind to the host cell membrane and release its contents inside, infecting the host cell.

Scientists have wanted to learn as much as they can about the Sars-CoV-2 spike protein, because it's where an infection starts, and its characteristics could have critical implications for the development of vaccines and therapeutics; this protein triggers an immune response in people.

Researchers have now used advanced techniques including molecular dynamics simulations and cryo-electron tomography, a tool for generating high-resolution three-dimensional views of macromolecules to assess the molecular structure of the spike protein at nearly an atomic scale. The findings have been reported in Science.

The investigators found that the SARS-CoV-2 spike protein has a spherical portion, which contains regions that bind and fuse to the host cell receptor. This is linked 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," explained Martin Beck, European Molecular Biology Laboratory (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," added Gerhard Hummer, of 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."

In this work, 266 cryo-tomograms of about 1,000 different viruses, each carrying about 40 spikes apiece, were created. After dynamics simulations and subtomogram averaging - an image processing tool that combines the tomograms, the new structural information about the spike protein was revealed. The flexibility of the stalk lies with three 'joints' that act as its ankle, knee, and hip.

Colorized scanning electron micrograph of a cell heavily infected with SARS-CoV-2 virus particles (yellow), isolated from a patient sample. Image captured at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. / Credit: NIAID

"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," said Jacomine Krijnse Locker, group leader at the Paul-Ehrlich-Institut.

Antibodies targeting the spike protein can prevent infection, neutralizing the virus, if they attach to the spike protein and prevent it from binding to a host cell. This work has shown that the entire spike protein, including the stalk, carries chains of sugar molecules called glycans. This gives the spike a kind of protective shield that helps prevent such neutralizing antibodies from binding to it.


Sources: AAAS/Eurekalert! via European Molecular Biology Laboratory, Science

About the Author
  • Experienced research scientist and technical expert with authorships on 28 peer-reviewed publications, traveler to over 60 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
AUG 17, 2020
Immunology
Nervous Protein Neuromedin B May Prevent Immune Reactivity
AUG 17, 2020
Nervous Protein Neuromedin B May Prevent Immune Reactivity
A protein produced by the nervous system seems to play a role in regulating the immune system. For people with inflammat ...
SEP 11, 2020
Genetics & Genomics
A Better Understanding of Telomere Length Throughout the Body
SEP 11, 2020
A Better Understanding of Telomere Length Throughout the Body
Telomeres cap the ends of chromosomes. They work to protect the chromosomes from degradation, and are known to get short ...
SEP 11, 2020
Cell & Molecular Biology
How Variants Affect Gene Expression Across Cell Types
SEP 11, 2020
How Variants Affect Gene Expression Across Cell Types
The Genotype-Tissue Expression (GTEx) Consortium, has produced multiple papers that have provided new insight into human ...
OCT 13, 2020
Microbiology
Bacterial Biofilms Can Take on Some Animal-Like Characteristics
OCT 13, 2020
Bacterial Biofilms Can Take on Some Animal-Like Characteristics
Bacteria are everywhere, even inside of our bodies, and they are thought to date back to the early days of life on Earth ...
OCT 18, 2020
Genetics & Genomics
'Silent' Mutations Might Have Given SARS-CoV-2 an Edge
OCT 18, 2020
'Silent' Mutations Might Have Given SARS-CoV-2 an Edge
The pandemic virus SARS-CoV-2 is thought to have originated in bats, like many viruses. To make the leap and infect anot ...
OCT 22, 2020
Cell & Molecular Biology
How a Gene Variant Raises the Risk of Multiple Sclerosis
OCT 22, 2020
How a Gene Variant Raises the Risk of Multiple Sclerosis
Now that sequencing the whole human genome is easier, faster, and cheaper than it used to be, scientists have been able ...
Loading Comments...