Amino acids have long been known to improve the stability and solubility of proteins. Amino acids might be added to insulin, for example, to maintain shelf-life and stop undesired chemical reactions from occurring before it's used. Researchers have now discovered how this works, and have revealed that all small molecules have a stabilizing influence in solution. The findings have been reported in Nature.
"When suspended in solution, proteins are constantly changing shape around a central form, and so the prevailing theory has been that amino acids help keep proteins from misfolding," noted first study author Ting Mao. "Now, we show that this is not the case. In fact, the stabilizing effect of amino acids has little to do with biology but is rather a general property of all small molecules in relation to larger particles, known as colloids, in solution."
Amino acids are strung together and folded into complex shapes to form many different molecules, like proteins, which carry out many crucial biological functions. But individually, amino acids are not very large, and they can affect larger molecules by preventing or screening passing interactions between larger molecules.
Meanwhile, salts can screen molecules that repel each other.
"What we have discovered is that amino acids are essentially the anti-salt, because they have an opposite screening effect. You can even see this in nature: it has been shown that when a plant is watered with salty water, its cells will produce more amino acids to help stabilize them as they become stressed by the increased salt concentration," explained co-corresponding study author Quy Ong, an EPFL scientist.
The investigators also suggested that amino acid concentrations should be reported when experiments are described in publications, just as salt concentrations are typically noted.
They also want to find ways to apply this knowledge. "We want to understand how small molecules like amino acids are central to healthy biological function...our goal is ultimately to predict which molecules can stabilize which proteins and how much, something that is currently done by trial and error in biomedical research,” added co-corresponding study author Professor Francesco Stellacci.
Sources: École Polytechnique Fédérale de Lausanne (EPFL), Nature