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.

As described in 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 on 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.

Solving the structure of the protein proved difficult, the scientists say, because F is an unusual protein that exists in two different forms, including the metastable shape that it adopts before it harpoons a cell and collapses into its stable post-fusion conformation. Solving the metastable structure was difficult because the anchoring of F to the virus surface (or membrane) is important for holding F in this active state. The protein's structure could not be solved unless it was in the membrane, but solving a protein structure like this required that it be separated from the membrane.

To accomplish this, the scientists used a bit of molecular trickery. They replaced the part of the protein that is embedded in the viral membrane with an engineered piece of protein that acts as a substitute. Thus, the F protein was stabilised in its pre-fusion form and could be crystallised. Then, using the Advanced Photon Source at the US Department of Energy's Argonne National Laboratory, the research team employed high intensity x-rays to obtain data from the crystals, which they then interpreted in order to reconstruct the structure of the F fusion protein.