Protein Structure: Researchers Found How Viral Protein Suppresses Immune Protein

The innate immune system, the first line of defense against pathogens and noxious chemicals, detects invasive pathogens and activates defense mechanisms to eliminate them. The defense system is made up of an array of receptors that are in charge of recognizing specific molecular conformations of the invasive. Among the molecules bound by these receptors, the RIG-I-like receptors in the cytoplasm of infected cells specifically bound these viral nucleic acids. One of these is MDA5, which polymerizes into filaments on long double-stranded RNAs that indicate the presence of RNA viruses. RIG-I itself binds to shorter terminal segments of viral RNAs.

Pathogens, however, trigger kinds of tricks to block this process: viruses have come up with many ways to avoid triggering immune defense measures.

In this Jan., a new study revealed this similar process of measles virus and why MDA5, but not RIG-I, is inhibited by the V protein, which is only through a hairpin-like protein structure. They made measles as an instance, which produces V protein and then the protein binds particularly to MDA5 and one of the RIG-I-like receptor. As a result, it damages the virus-infected cells recognition via adaptive immune system.

It is this competition between viral and cellular proteins that dramatically affects the distribution and the virulence of viral pathogens.

The researchers said that a hairpin opens up the receptor and they can crystallize the complex formed by the V protein and MDA5 for the first time, and they have determined its three-dimensional structure in detail. This structure also clarifies the mode of action of the V protein.

The analysis revealed that it inserts a hairpin loop into the core secondary structure of MDA5, unfolding the protein and allowing V to bind to a segment that is normally buried in the interior of the molecule. This in turn prevents MDA5 from forming filaments and signaling the presence of viral RNA.

 

This finding was completely unexpected: This internal sequence is different in RIG-I and this is the reason why RIG-I is not targeted by the viral product. This research brought more insight into the mechanisms viral proteins use to inhibit host protein function. It may also open opportunities for new therapeutic interventions and others.

 

 

Article Link: Protein Structure: Researchers Found How Viral Protein Suppresses Immune Protein