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Scientists identify molecular structure of key viral protein

Scientists at Northwestern University have determined the molecular structure of a viral protein, the parainfluenza virus 5 fusion (F) protein. The parainfluenza virus 5 is part of a family of viruses (paramyxoviruses) that causes everything from pneumonia, croup and bronchiolitis to cold-like illness and is responsible for many hospitalizations and deaths each year. The results will be published Jan. 5 by the journal Nature.

Details of the protein's structure in its metastable state -- the state of the protein on the virus surface responsible for infecting cells -- has significant implications for developing improved protein-based vaccines, designing novel anti-viral agents and understanding the entry mechanisms of other viruses. Knowing the structure of the F protein will aid understanding of all members of the paramyxovirus family, which are among the most significant human and animal pathogens, causing both respiratory and systemic disease.

"The development of antiviral drugs is helped by knowledge of the structure, shape and mechanism of the target molecules, which is what we can now provide for the F protein," said Theodore S. Jardetzky, professor of biochemistry, molecular biology and cell biology, who co-led the study. "Knowing how the virus gets into the cell will allow us to better inhibit this key part of the viral life cycle."

Tens of thousands of different proteins are at work in the human body, each folded into a very specific shape to do its job properly. Most proteins have just one shape for their lifetimes, but a handful -- in particular, proteins associated with enveloped viruses such as HIV, influenza virus and the paramyxoviruses -- have two dramatically different shapes, one before the virus attacks and enters a cell and one after. The parainfluenza virus 5 fusion protein is one of these. It is the change of the fusion protein from the initial metastable state to the post-virus entry state that drives the fusion of viral
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Source:Northwestern University


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