The laboratory of structural biologist Yizhi Jane Tao produced the first full-length structure of the matrix protein found in the ISA virus, reports Science Daily. And because the protein's structure and function are so similar to what has been found so far in influenza viruses, Tao expects they will be useful in determining the mechanisms of human viruses as well.
"This virus and all the influenza viruses belong to the same family, so they assemble in a very similar way," said Tao, of Rice University, Houston, Texas. "Although this protein is from a fish-infecting virus, it will give us insight as to how the matrix proteins support the assembly of other viruses."
Fragile matrix protein
The discovery is detailed in the Proceedings of the National Academy of Sciences.
Tao's lab specialises in X-ray crystallography and other techniques to reveal the basic structures of molecules like the fragile matrix protein dubbed M1. Many attempts to define the complete structure have failed because the protein has two major sections: the N and C domains.
Because the thin strand of residues that holds the domains together falls apart so easily, researchers until now have only been able to capture N domain structures through crystallisation.
The elbow-shaped structure of the M1 found in the ISA virus has six tightly packed alpha helices that make up the N domain and closely resemble those found in strains of influenza A. On the other side of the flexible hinge, the "elbow," lies the C domain with four alpha helices.
Tao said having the complete structure of the protein will help researchers determine how it and others like it polymerise into a protective shell and associate with the membrane. "Knowing the structure of only one domain, we could not understand how matrix proteins interacted with each other to form the shell," she said. "The interaction involves both domains."
"M1 helps to support the shape," Tao said. "That is a major function for any matrix protein. The matrix also helps to incorporate the viral RNA. Presumably, if there's no matrix protein, you end up with an empty vesicle."
A treatment that addresses M1 would have to find and invade the virus-infected cells.
"But if there's a chemical that can interrupt the self-association of M1 proteins, it's going to be very useful," Tao said. "I don't think it matters which domain it binds, as long as it prevents the shell from forming. This could be a valid target."