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Scientists identify molecular structure of key viral protein

ein opens the inside of the virus to the inside of the cell, delivering the viruses genetic information into the cytoplasm of the cell to infect it."

In the process the protein moves from its first folded state, the metastable state (pre-fusion), to its second, final and very stable state (post-fusion), undergoing a dramatic change of shape. "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," said Jardetzky.

"The metastable protein is a one-time-use machine," said Lamb. "It does its work and then it's finished, spent. And you want the protein to be triggered at the right time and in the right place for fusion: when the virus binds to the cell's surface."

The research team determined the pre-fusion structure by imaging crystals of the protein, using the extremely brilliant X-rays produced by the Advanced Photon Source (APS) synchrotron at Argonne National Laboratory in Illinois and at the Howard Hughes Medical Institute beamlines at the Advanced Light Source in Berkeley, Calif.

First the researchers had to make the protein, which included pulling a scientific trick on the protein to get it to fold properly and keep it in its metastable state. Because the molecules of the protein are so small they could not be imaged directly. Instead, the researchers used many of these molecules to create a crystal that could be imaged.

Using the method of X-ray diffraction, they bombarded the crystal with X-rays, which bounced off the atoms within the crystal. By collecting and analyzing this information, Jardetzky, Lamb and their colleagues determined the location of each atom within the structure.

Jardetzky credits the very high intensity X-rays for enabling the researchers to image the structure at 2.85 angstroms. (An angstrom is one ten-billionth of a meter, or
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Source:Northwestern University


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