Scientists at the Scripps Research Institute have uncovered the structure of a critical protein from the Ebola Virus that allows viral entry in human cells.
"This structure reveals how this critical piece of the virus is assembled and helps explain how the pathogen evades and exploits the human immune system," explained Erica Ollmann Saphire, the Scripps Research scientist who led the five-year effort.
There is currently no cure for Ebola hemorrhagic fever. The virus is spread when people come into contact with the bodily fluids of someone who is already infected. Most ultimately die from a combination of dehydration, massive bleeding, and shock.
Described in the cover article of the July 10, 2008 issue of the Nature magazine, the research reveals the shape of the Ebola virus "spike" protein, which is necessary for viral entry into human cells. The Scripps discovery of this structure provides a major step forward in understanding how the deadly virus works, and may be useful in the development of potential Ebola virus vaccines, or treatments for those infected.
The Role of Fluidigm's TOPAZ Protein Crystallization System
Scripps researchers generated more than one hundred versions of the protein for crystallization studies. TOPAZ screening chips were used to identify crystallization conditions, and vapor diffusion methods were used to reproduce crystals suitable for X-ray diffraction. The crystals were further optimized and X-ray diffraction data was ultimately collected to 3.4 Ångströms.
"It is difficult to produce a lot of this protein, but the possibility of screening on a small scale helped us find a GP-antibody complex that would crystallize reproducibly," said Dr. Ollmann Saphire.
TOPAZ screening chips are capable of running up to 768 experiments in parallel using only 1 microliter of protein per 96 conditions. The TOPAZ system also includes an effective analysis software for scoring crystals and managing the vast amount of data obtained from crystallization experiments.
A press release from the Scripps Research Institute describing their discovery in greater technical detail is available at: http://www.scripps.edu/newsandviews/e_20080714/ebola.html