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Scientists identify molecular structure of key viral protein

al and cellular membranes, permitting entry of the viral genome into the cell.

"What we've learned about the structure of the parainfluenza virus 5 fusion protein will be directly applicable to the whole family of paramyxoviruses," said virologist Robert A. Lamb, John Evans Professor of Biochemistry, Molecular Biology and Cell Biology and co-leader of the study. "The family includes viruses that cause measles, mumps, bronchitis, pneumonia, canine distemper, croup and Newcastle disease, which kills chickens. Measles still causes huge numbers of deaths worldwide. And while HIV, influenza and SARS are not in the same family, the viruses do share a mechanism similar to that used by paramyxoviruses for entering the host cell."

The parainfluenza virus 5 is also closely related to two recently discovered and deadly viruses called Hendra and Nipah viruses, which are classified as select agents of concern for biodefense.

The pre-fusion structure of the F protein combined with the structure of the protein in its post-fusion state, which was determined and reported earlier in 2005 by this same research team, gives scientists a complete picture of how the paramyxovirus F protein works to infect the cell.

The F protein belongs to a group of fusion proteins (class I) that exist in two states: the metastable or pre-fusion state and the post-fusion state. This is only the second time that both the pre- and post-fusion structures have been determined for a class I viral fusion protein. The first was for the influenza virus, completed in 1994. While a lot of research is currently being conducted on the HIV fusion protein, its two structures -- and an understanding of how the protein works -- remain incomplete.

"The protein we studied," explained Lamb, an Investigator for the Howard Hughes Medical Institute, "is sequestered on the virus and is responsible for bringing about a membrane merger or fusion of the viral and cellular membranes. Th
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Contact: Megan Fellman
fellman@northwestern.edu
847-491-3115
Northwestern University
4-Jan-2006


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