Thursday, 24 March 2011

Hungry Hungry Hemagglutinin

The 1918 influenza pandemic killed over 20 million people. Hemagglutinin is one of the insidious proteins directly responsible for this virus' destructive power. It is the virus' grappling mechanism for attaching to a healthy cell. The virus is bristling with these proteins, ready to fasten to a cell, and subsequently annihilate it.

The human form of the disease is thought to have avian roots. In birds, hemagglutinin attaches primarily to α2,3 linkages of sialic acid to galactose. The major strains of human influenza use hemagglutinin to bind to α2,6-linked sialic acid, which is plentiful in the human respiratory tract. A small mutation in hemagglutinin can convert the protein from preferential binding of α2,3 linkages to α2,6 linkages. The mutation at the sites responsible for binding the sialic acid removes a hydrogen bond system from the avian version, which effects a small structural change. Thus, the preferential binding changes. This explains the species crossover that must have happened at some point. (1) , (2)

Once the virus attaches to the sialyl species, the virus is pulled into the endosome, where the cell adds acid in an attempt to digest the bound protein. 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, eagerly seeking soft membrane flesh to sink their teeth into. (2) The hooks attach to the cell membrane, locking the virus in place. The protein then changes conformation, 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.

Image courtesy of PDB


(1) Gamblin, S. J.; Haire, L. F.; Russell, R. J.; Stevens, D. J.; Xiao, B.; Ha, Y.; Vasisht, N.; Steinhauer, D. A.; Daniels, R. S.; Elliot, A.; Wiley, D. C.; Skehel, J. J.
Science 2004, 303, 1838 -1842.

(2) 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.

(3) Han, X.; Bushweller, J. H.; Cafiso, D. S.; Tamm, L. K.
Nat Struct Mol Biol 2001, 8, 715-720.

Tuesday, 1 March 2011

Hemagglutinin: Grappler of Doom

Behold... Hemagglutinin! It is one of the deadly tools of the influenza virus, killer of millions!

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.

This evil looking red is perfect for a virus protein.

And check out this snazzy, gray background... classy.