Protein
Crystal Growth
There are over 300,000 proteins, the building-blocks of life, in the human body alone. Yet we only know the structure of less than 1% of these proteins. In the microgravity environment aboard the space shuttle, we can grow protein crystals of high quality, such as shown at the left. When we return these to the Earth, we can then study the crystals with a process called "X-ray crystallography" to map the protein, and learn more about what its structure is like. Like learning the shape of a piece of a jigsaw puzzle, by understanding the structure of proteins in the human body, scientists can then learn how these proteins fit into the overall biology of humans, and how the proteins work in the body.
MSL-1 carries three experiments sponsored by NASA/Marshall, one to grow crystals in tiny trays, (the Protein Crystallization Apparatus for Microgravity, or PCAM) one to grow crystals in drops at the tips of triple-barrel syringes, (Second-generation Vapor Diffusion Apparatus, or VDA-2) and one to use diffusion in a hand-held experiment (Hand-held diffusion test cells, or HH-DTC). All are pictured at left, click for larger image.
Why go after these proteins?
Many diseases involve proteins either directly or indirectly. These can be in the form of hormonal irregularities, toxins produced by invading organisms, or proteins an invading organism needs to survive, prosper, and replicate. An example of this last form include angeogenin, a protein secreted by tumor cells that encourage the growth of blood vessels toward the tumor, and HIV protease, a protein required by HIV to manufacture the proteins it needs to replicate.
In the past, effective disease fighting agents were discovered largely by trial and error. This required literally tens of thousands of trials before a chemical with the desired biological activity was discovered.
Now, however, we can map the 3-dimensional structure of proteins through X-ray crystallography. Once the structure of a particular protein is known, it becomes much easier to think about how one might block its activity in the human body, for example, much in the same way as it is easier to design a key if the details of the lock were known.
Of course, this analysis requires that we have a very high-quality protein crystal in hand for accurate mapping.
Why grow crystals in space?
With the recent advances in powerful X-ray sources and supercomputers for solving the complex three-dimensional structures, the limiting step in this technology is the ability to crystallize specific proteins with sufficient size and crystalline quality to obtain the high resolution X-ray diffraction patterns needed to solve their structure. For reasons that are not totally clear, crystals often will grow larger and with much better internal order, if made in microgravity. The improved X-ray diffraction data from these space-grown crystals has allowed researchers to refine structures in much more detail than ever before, and has allowed the structure of some proteins to be determined for the first time.
What has crystal growth in space provided so far?
Since 1984, protein crystal growth experiments have been performed on over 20 shuttle missions. From over 33 proteins, ranging from insulin to HIV reverse transcriptase, the microgravity environment for crystal growth improved over the best-case Earth-grown crystals in the following ways:
- Larger Crystals in 45.4% of the cases
- New Crystal Structures in 18% of the cases
- At least a 10% increase in the X-Ray Crystallography Brightness in 58% of the cases
- Less thermal motion in 27.2% of the cases
- An X-Ray Crystallography resolution improvement of ~0.3 Angstroms in 42.4% of the cases
- An X-Ray Crystallography resolution improvement of 0.3 to 0.5 Angstroms in 9.9% of the cases
- An X-Ray Crystallography resolution improvement of 0.5 to 1.0 Angstroms in 9.9% of the cases
In the improvement of resolution, a 1 Angstrom improvement can mean the three-dimensional structure can be determined and atomic positions in the macromolecule can be resolved.
Some figures on the cost of disease:
The social costs of American illnesses and disease are estimated at $900 billion annually.
- Cancer
- $104 billion per year according to the American Cancer Society
- Proteins such as epidermal growth factor, apocrustacyanin C, interferon a-2b play important roles in the disease.
- Diabetes
- $92 billion per year according to the American Diabetes Association
- On USML-2, an artificial sweeter called Thaumatin was crystallized in space
- Alcoholism
- Affects more than 18.5 million Americans according to Alcoholics Anonymous
- Liver transplants cost more than $250,000 On USML-2, the enzyme responsible for metabolizing alcohol (alcohol dehydrogenase) in the liver was crystallized in space.
- AIDS
- Projected to affect more than 40 million people world-wide
- HIV protease, HIV reverse transcriptase were crystallized in space The latter showed significantly improved internal ordering in the space-grown crystals
- Alzheimer's
- Projected to cost $215 billion per year by 2015 according to the American Alzheimer's Foundation
- Proteins involved in the death of cells, such as CcdB are part of ongoing experiments Most recently flown on USML-2 in 1995.
- Chagas Disease
- This parasitic disease affects many people in Latin and Central America.
- On MSL-1, in cooperation with a consortium of nations from this region, including Mexico, Costa Rica, and - for the first time - Brazil, proteins related to this disease will be crystallized for study on the ground after the mission.
Did You Know That:
At a rate of six shuttle flights per year, each successfully producing crystals to reveal the structure of 1,000 different proteins per flight, we would not learn the structure of all the human proteins for another 35 years???
