A Look at What Happens to Supercooled Proteins

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The human body functions best within an optimal temperature range. If temperatures are raised or lowered beyond this range, bodily functions can be altered or cease altogether. On a molecular level, the same is true.

Research regarding how temperature changes—particularly suboptimal temperatures—affect the various components of the human body has been ongoing for decades. However, new research involving individual cells at extremely low temperatures has revealed a great deal about how they change and continue to function while cooled.

How Protein Folding Affects Function

Like the rest of the body, proteins function best within a relatively narrow temperature range. Under normal conditions, the amino acids that serve as the building blocks of a protein interact with one another and cause the protein to fold. At optimal temperatures, this folding allows the protein to reach its final structure and interact appropriately with other cell elements around it—hence fulfilling its purpose within the cell.

When conditions within the cell are not optimal, proteins can undergo changes that affect how they function within the cell. These negative cell conditions can cause proteins to denature, or undergo physical alteration. When proteins denature, they unfold from their primary structures, which can expose some amino acids and hide others. When this occurs, protein unfolding negatively affects the extent to which proteins perform their work.

New Insights

While it’s no secret that proteins change and denature as they are exposed to low temperatures, scientists at Princeton University recently made new discoveries regarding what happens under supercooled conditions. During the experiment, researchers suspended a 20-amino-acid protein, Trp-cage, in water supercooled to 210K—nearly -82°F. As expected, the proteins denatured once temperatures deviated from the optimal range; however, what happened next was surprising.

As temperatures approached 194K, the once-denatured proteins actually refolded instead of remaining in their unfolded state. This supercooled, folded state was not identical to the natural folded structure of the protein but was very similar. Primarily, the most significant helix feature of the folded protein reappeared, accompanied by a hydrophobic core.

In an attempt to explain the differences between the initial, folded structure and this new, refolded structure, researchers began to analyze the way the surrounding water molecules interacted with the protein. It was discovered that, while the water remained liquid, it did transform from a high-density state to a low-density state at the same temperature. In this state, the water molecules were organized in such a way that they no longer solvated the core of the protein, which collapsed and refolded.

Moving Forward

While proteins will never reach this level of supercooling within the human body, there is value in studying their behavior at extremely low temperatures. Applications such as cryo-preservation of embryos, organs, and other human cells as well as cryo-microscopy could benefit from further knowledge about how the associated proteins behave at these temperatures.

As researchers gain knowledge about protein behavior at all temperatures, a more complete understanding of how proteins function will become available. These insights could lead to the ability to develop therapies for protein function-based diseases or even ways to halt them altogether. With continued investigation, the future of protein research remains bright.




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