Beautiful but Deadly

Hemagglutinin is a beautiful but deadly protein. It was responsible for the virulence of the 1918 Spanish Flu, which experts think killed approximately 50 million people^[1]. Researchers have spent countless years attempting to defeat it, yet it keeps evolving to evade every countermeasure that the body can throw at it. It exists in a trimeric form with rotational symmetry along the central axis and has specially adapted head and tail regions that allows it to thwart the body's immune system.

Hemagglutinin Trimer-Side View (source: PyMOL 4EEF)

Hemagglutinin Trimer-Top view (source: PyMOL 4EEF)

In order for viruses to invade human cells, the Hemagglutinin must bind to the to certain sugars on the cell membrane^[2]. The virus is then carried inside an endosome of the cell, where the cell attempts to destroy the virus by lowering the pH of the compartment^[3]. Yet instead of destroying the virus, the pH induces refolding of Hemagglutinin, which allows it to bind the cell membrane with the viral membrane and open it up for the viral DNA to flow into the cell^[4].

ph Induced Refolding (source: PDB protein of the month)

Thus in its efforts to destroy the invader, the cell has only served to help the virus in its quest and will serve as a site for the virus to mount a continued attack on the rest of the body.

Hemagglutinin has resisted efforts to find a vaccine, as it is constantly mutating. The head region is constantly adapting to new environments, always trying to stay at least one step ahead of the body's immune system^[5]. They are many different strains, from the dreaded Spanish Flu (H1N1) to the potentially dangerous Swine Flu (H1N1/09) to the perhaps overhyped Bird Flu (H5N1). Each of these have small variations in the Hemagglutinin, typically in the head region. there is currently hope for drugs that can treat these strains through the production of drugs that are capable of targeting the conserved stem regions, yet such drugs are still a long ways off^[6]. Until then, we will just have to stock up on chicken noodle soup and ginger-ale.

[1] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2692245/
[2] http://www.rcsb.org/pdb/101/motm.do?momID=76
[3] http://www.pnas.org/content/105/46/17736.full
[4] http://www.pnas.org/content/105/46/17736.full
[5] http://www.sciencemag.org/content/332/6031/816.full
[6] http://www.sciencemag.org/content/332/6031/816.full