Structure of Viral Fusion Protein

Virologists have used x-ray diffraction crystallography techniques to determine the structure of the parainfluenza virus fusion (F) protein in its metastable (pre-fusion) state.

Investigators at Northwestern University (Evanston, IL, USA)
stabilized the pre-fusion form of the F protein by the addition of a carboxy-terminal trimerization domain. Then, they used advanced x-ray crystallography techniques to establish the structure of the F protein to a resolution of 2.85 angstroms. The details of their study were published in the January 5, 2006, issue of Nature.

The virus relies on F protein for attachment and penetration of the host cell membrane. The x-ray diffraction data showed that there were profound conformational differences between the pre- and post-fusion states, involving transformations in secondary and tertiary structure. "The protein in its metastable state has a very specific job to do--to enable infection of the cell--and it does this by essentially acting as a harpoon that shoots into the cell's membrane to bring about the fusion,” explained senior author Dr. Theodore S. Jardetzky, professor of biochemistry, molecular biology, and cell biology at Northwestern University.

"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 Dr. Jardetzky. "Knowing how the virus gets into the cell will allow us to better inhibit this key part of the viral life cycle.”






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