glycan – BioQuakes

The wonderful jumble of molecules that make up living things is so complex that biologists have overlooked an entire class of them, until now. This missing piece of biochemistry is neither rare nor difficult to find, it’s just that no one had thought of looking for it before. Researchers at Stanford University have discovered a new kind of biomolecule that could potentially play a significant role in the biology of all living things. This newfound biomolecule, consisting of RNA modified by sugars, could be present in all forms of life and might possibly contribute to autoimmune diseases.

Glycoprotein (CD4)

This newly discovered biomolecule is called glycoRNA. It is a small ribbon of ribonucleic acid with sugar molecules, called glycans, dangling from it. Up until this point in time, the only kinds of similarly sugar-decorated biomolecules known to science were lipids and proteins. These glycolipids and glycoproteins appear everywhere in and on animal, plant and microbial cells, contributing to a wide range of processes essential for life.

After documenting the presence of the newly discovered glycoRNA in human cells, Ryan Flynn (the study’s lead author) and colleagues searched for it in other cells. They found glycoRNAs in every cell type they tested which consisted of human, mouse, hamster, and zebrafish. The presence of glycoRNAs in different organisms suggests they perform fundamentally important functions. Furthermore, the RNAs are structurally similar in creatures that evolutionarily diverged hundreds of millions to billions of years ago. This suggests glycoRNAs could have ancient origins and may have had some role in the emergence of life on Earth, The function of glycoRNAs is not yet known, but it requires further research and study as they may be linked to autoimmune diseases that cause the body to attack its own tissues and cells. For example, the immune systems of people suffering from lupus are known to target several of the specific RNAs that can compose glycoRNAs.

This is exciting and interesting because it means that glycoRNAs can participate directly in cell-to-cell communication. Previously, it was believed that this was prohibited for RNAs that were not believed to play a role on the cell surface. While glycoRNAs functions are still a mystery, this discovery will hopefully lead to many more answers soon, possibly about some people’s troublesome immune systems.

In a study done by Rommie Amaro and colleagues at the University of California San Diego, Maynooth University (Ireland), and the University of Texas at Austin, it has been discovered that certain Glycans, or a sugar molecule chain bound to the SARS-CoV-2 spike proteins, could be a real reason that SARS-CoV-2 can easily enter our bodies.

The SARS-CoV-2 structure, featuring more detailed and realistic images of the spike proteins.

In order for a human– or a host cell– to be infected with COVID-19, the actual virus (SARS-CoV-2) must infiltrate the host cells. As SARS-CoV-2 is covered in spike proteins, these proteins dock up with a host cell receptor called ACE2, which is embedded in the cellular membrane. In order for the virus to successfully dock with the receptor, it must change its shape in order to expose the Receptor Binding Domain (RBD), or exactly where the spike protein docks with ACE2.

At the specific spike protein/ACE2 docking points, the spike proteins are covered in Glycans, or sugar molecules. These glycans have the ability to protect the virus from the host cell’s immune system. Relating the importance of the glycans and the immune system to our class, we have heavily researched the roles of sugars in molecular processes and pathways and the functions of the immune system. With this knowledge, we are able to see, recognize, and understand how powerful and prevalent the glycan is in guarding the virus against our usually strong, organized immune system attacks. As the scientists in the study processed the information about the glycans, they were intrigued to discover how it could possibly lead to easier rates of infection.

To begin, they used dynamic computer models to simulate the glycan-covered spike proteins docked to the ACE2 in the cell membrane. They were able to deduct that the glycans help optimize the spike protein’s effort to expose its RBD. Thus, the glycans actively allowed easier infection through an easier docking experience. However, they also uncovered that the glycans only bound to certain spike proteins, meaning that the immune system, but specifically antibodies, could attack the virus at these docking points. Posing as an extremely positive discovery, the absence of glycans in certain docking points inspired the team to see if they could get rid of the glycans in total. Through Biolayer Interferometry, or technology that allows you to record biomolecular interactions, they were able to successfully mutate the spike protein so it didn’t have glycans anymore– thus, reducing SARS-CoV-2’s ability to bind to ACE2.

The concept of removing the glycans from the spike proteins has been a major point of research in vaccine production. Although vaccines being made by Pfizer and Moderna are revolved around MRNA, ideas like debilitating the virus-protecting glycans are extremely revolutionary and could lead to possible amazing breakthroughs in the future.

BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: glycan

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