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Molecule of the Month: Influenza Neuraminidase

by PhilipJ on 13 May 2009

influenza neuraminidaseInfluenza virus is continually changing and every decade or so, a dangerous new strain appears and poses a threat to public health. This year, there has been an outbreak of a new strain of H1N1 flu, more commonly known as swine flu. The H1N1 designation refers to the two molecules that cover the surface of the virus: hemagglutinin and neuraminidase. Together, these two molecules control the infectivity of the virus. Hemagglutinin plays the starring role as the virus approaches a cell, binding to polysaccharide chains on the cell surface and then injecting the viral genome into the cell. Neuraminidase, on the other hand, plays its major role after the virus leaves an infected cell. It ensures that the virus doesn’t get stuck on the cell surface by clipping off the ends of these polysaccharide chains.

Neuraminidase, shown here at the top from PDB entry 1nn2, is composed of four identical subunits arranged in a square. It is normally attached to the virus surface through a long protein stalk (not shown). The active sites are in a deep depression on the upper surface. They bind to polysaccharide chains and clip off the sugars at the end. The surface of neuraminidase is decorated with several polysaccharide chains (seen extending upwards and downwards in this structure) that are similar to the polysaccharide chains that decorate our own cell surface proteins.

As with hemagglutinin, neuraminidase comes in a variety of subtypes named N1-N9. These subtypes are defined by their interaction with antibodies: all of the variants within a given subtype will be neutralized by a similar set of antibodies. These subtypes are one of the causes of the continual effectiveness of influenza. Some of the subtypes promote infection in people, others promote infection in birds, and others target pigs and other mammals. As viruses spread and infect different organisms, they can mix and match different subtypes, randomly building new combinations and occasionally coming up with particularly lethal combinations.

To read more about this timely molecule of the month, click here for the rest by David Goodsell at the RCSB PDB.

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