Wednesday, 27 April 2011

Hemagglutinin Wants You! (So It Can Help Kill Your Cells)

That's right, hemagglutinin wants you, or at least the α2,3 linkages of sialic acid to galactose present in your respiratory tract (it likes to bind to those). Hemagglutinin is a key player in the influenza virus' mission to destroy all humans. In the pandemic of 1918, it humbly assisted in the deaths of over 20 million people. How did it accomplish this you ask? By acting as an insidious grappling device eager to sink its vicious fangs into an unsuspecting, healthy cell. The flu virus is bristling with these malevolent proteins, allowing for attack from any angle.

Image courtesy of PDB

As the virus draws near a healthy cell, hemagglutinin binds to protein-bound sugars in the membrane, shown in green in the above image. The cell then attempts to digest the intruder, taking the virus into the endosome and adding acid. Little does the cell know it is engendering its own demise. Acid causes hemagglutinin to refold itself into a conformation exposing its membrane hungry hooks (shown in red), eagerly seeking soft membrane flesh to drive their ravenous barbs into. (1) The hooks attach to the cell membrane, locking the virus in place. The protein then changes conformation again, pulling the virus in close to the cell membrane, ultimately allowing them to fuse. Thus, the virus RNA is unleashed into the cell, where it can wreak havoc and deal out death and destruction.

Now I know what you might be thinking, "But we have antibodies to save us from the evil clutches of this malicious protein." Hemagglutinin cackles at your sad hope. All it has to do to render itself immune to these antibodies is to move around a couple carbohydrates on the protein surface. Thus, this new strain can evade detection and proceed on its murderous rampage.

Now that we've covered the process by which hemagglutinin will kill your cells, let us bask in its deadly majesty...

Marvel at its perilous helices and treacherous beta sheets...

Its structure has been instrumental in the eradication of trillions of living cells... and yet, it has a certain pernicious beauty about it.

After such a display of elegance and terror, how could you not vote for this as protein of the year? As you make your decision, remember, hemagglutinin is ready and able to attack new cells all the time... Will yours be next?


(1) Sauter, N. K.; Bednarski, M. D.; Wurzburg, B. A.; Hanson, J. E.; Whitesides, G. M.; Skehel, J. J.; Wiley, D. C. Biochemistry 1989, 28, 8388-8396.