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Structure of viral harpoon protein reveals how viruses enter cells

A team of Northwestern University researchers has solved the structure of a molecule that controls the ability of viruses of the paramyxovirus family, including the viruses that cause measles, mumps, and many human respiratory diseases, to fuse with and infect human cells. Determining the structure of this molecule and its role in the viral fusion mechanism may aid the development of drugs and vaccines that target these types of viruses, say the scientists, whose work was funded by the National Institute of General Medical Sciences (NIGMS) and the National Institute of Allergy and Infectious Diseases (NIAID), both parts of the National Institutes of Health (NIH).

As described in the latest issue of the journal Nature, this large protein, called F, studs the surfaces of certain RNA viruses that are encased in a membrane envelope. As soon as such a virus comes in contact with a cell it can infect, the F protein changes shape and extends like a harpoon into the outer membrane of that cell. Then the protein undergoes a conformational (shape) change and collapses upon itself, pulling the virus against the host cell and fusing the viral membrane with the target cell's membrane. The fusion unleashes the viral RNA into the cell, which then hijacks the cell's machinery to make and spread more virus.

"Because of F protein's central role in viral infection, solving the structure of this critical protein is truly a great advance in biomedical science," says Elias A. Zerhouni, M.D., NIH director.

Even though the basic concept of viral fusion has been understood for some time, the complete conformations of the structures of the before- and after-fusion forms of the F protein had eluded scientists until the recent work of the Northwestern team, which was led by Theodore Jardetzky, Ph.D., and Robert Lamb, Ph.D., Sc.D. What has allowed Drs. Jardetzky, Lamb and their colleagues to understand these new mechanistic details is the fact that they determined the
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Contact: Jason Socrates Bardi
jbardi@niaid.nih.gov
301-402-1663
NIH/National Institute of Allergy and Infectious Diseases
4-Jan-2006


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