Chemists reveal the structure of influenza B protein, A team of chemists has found an important structure of flu proteins, a discovery that could help researchers develop drugs that block proteins and prevent the spread of viruses.
The protein known as BM2 is a proton channel that controls the acidity of the virus and helps release its genetic material into infected cells. If you can block this proton channel, you can inhibit flu infections with the help of a researcher, an MIT chemistry professor, and a senior study author. Now the team of chemists reveal the structure of influenza B protein.
The structure of the dissolution of this protein atom is exactly what chemists and medical pharmacists need to develop the small molecules that block it.
There are three classes of influenza viruses – A, B and C – and each produces a different version of the M2 protein. M2 is the ion channel that transports protons through the outer membrane of the virus, which is called a lipid envelope.
These protons usually penetrate the virus, making the inside more acidic.
This acidity helps the virus to integrate its lipid sheath into the cell compartment membrane, endosomes, which allows it to release DNA into the infected cell.
So far, most structural studies of M2 protein have focused on the M2 version found in influenza A. This is usually the most common form, especially at the start of the flu season. In this study, the researchers focused on the M2 version found in influenza B virus which usually dominates in March and April.
Unlike previous seasonal influenza patterns, however, B flu is unusually common this winter, accounting for 67 percent of all influenza cases reported at the U.S. disease control center. Last September. Chemists reveal the structure of influenza B protein.
The A and B versions of M2 differ greatly in their amino acid sequence. Hong and colleagues have begun to investigate the structural differences these proteins have and how these differences affect their function.
The main difference is that the protons of the BM2 channel flow in all directions, while the protons of the AM2 channel penetrate the virus envelope.
To study the structure of BM2, the researchers built it into a lipid bilayer like cell membrane and analyzed the structure using NMR atomic spectroscopy resolution.
Because of the difficulty in studying proteins embedded in membranes, very few high-resolution ion channels have been investigated.
Hong has previously developed several NMR techniques that allow him to obtain accurate structural information about proteins embedded in membranes, including orientation and distance between protein atoms.
The M2 channel consists of four spirals that run parallel across the membrane, and Hong found that the orientation of this spiral changes slightly depending on the pH of the medium outside the viral envelope. When the pH is high, the spiral tilts around 14 degrees and the channel is closed. When the pH drops, the spiral increases its tendency to around 20 degrees and opens like a scissor.
This scissor motion creates more space between the spirals and allows more water to flow into the channel.
Previous research has shown that when water flows into the M2 channel, amino acid histidine takes protons from the water at the top of the channel and passes them to the water molecules at the bottom of the channel, which then releases excess protons to the virions.
Unlike the AM2 channel, the BM2 channel contains additional histidine at the end of the Virion channel, which, according to the MIT team, explains why protons can flow through channels in all directions.
Once chemists know the structure of the open and closed BM2 channels at atomic resolution, they can try to find ways to block them.
There is a precedent for this type of drug development: amantadine and rimantadine, both of which are used to treat influenza A, work by clamping pores of AM2 channels and interfering with proton flow. However, these drugs do not affect the BM2 channel. Hong’s research team is currently investigating another function of BM2 that creates curvature in the lipid membrane to allow the progeny virus to be released from cells.
Preliminary studies show that some proteins that protrude from the membrane form structures called beta sheets which stimulate the membrane to bend inward.