Proteins are among the most-studied molecular structures in the living universe—and for a good reason. Not only do proteins form the building blocks of each cell for every living organism in all scientific kingdoms, but they power, activate, enable, and affect the vast majority of all biological functions. As a result, proteins are frequent targets for therapeutic interventions designed to halt the effects of disease. However, much care must be taken to ensure that proteins remain stable throughout the research and drug design process.
Why Does Protein Stability Matter?
Proteins are enormously important for drug design and other nanotechnology research. However, proteins must be kept stable while in lab storage, during research procedures, and especially after development as a therapeutic component used to treat human disease. While this is true for multiple reasons, the most important is the connection between protein structure and protein function.
Proteins interact with themselves and other surrounding molecules primarily by forming bonds. These bonds can activate molecular processes, transport molecules, and serve various other functions. However, when proteins are unstable—usually due to changing conditions within the cell, test sample, or the external environment—they can change in structure. A change in structure alters the binding sites exposed to other molecules and ultimately changes the way they perform their primary functions. If proteins do not function as expected due to poor cellular or storage conditions, they may behave differently and ultimately prove ineffective in the experimental phase or, worse, act dangerously during clinical trials as a component of a therapeutic drug.
Creating Protein That Does Not Denature
One of the most significant ways proteins change is via heat denaturation. This is the loss of functional structure due to high temperatures. Unfortunately, this prevents many helpful proteins from being used in therapeutic or other applications where heat is involved. Researchers participating in a collaboration between Japan’s Shinshu University and Princeton University in the United States have developed an innovative version of a building block protein that does not denature at high temperatures.
Previously, researchers developed a preliminary version of this protein (known as WA20), capable of building protein complexes with applications in biopharmaceuticals and nanotechnology. However, this protein had a relatively low denaturation temperature of 75℃, preventing it from use in many applications. Researchers believe they have solved the crystal structure issues within WA20 to develop a more stable artificial protein. They have named the new protein SUWA, or Super WA20, in honor of one of Japan’s most significant shrines—Suwa Taisha.
SUWA is considered hyper-stable and does not boil at 100°C like its predecessor WA20. Even more significantly, SUWA does not denature until 122°C. Researchers believe their stabilization of SUWA’s artificial three-dimensional structure—particularly the center of its helices—allows SUWA to resist denaturation where WA20 did not.
Future Potential
With its impressive stability, SUWA can withstand high-heat conditions often present in many experimental and therapeutic applications. Insights from developing this and other hyper-stable artificial proteins could lead to the successful development of proteins with characteristics designed to perform therapeutic functions as a component of pharmaceutical drug research. Researchers hope that in the future these hyper-stable SUWA proteins can construct solutions for many issues crucial to the human condition.
Resources:
https://www.eurekalert.org/pub_releases/2020-02/su-sah022820.php
https://www.karger.com/article/pdf/104678
https://pubs.acs.org/doi/10.1021/acssynbio.9b00501
http://chemistry.elmhurst.edu/vchembook/568denaturation.html
