Much like students at a club on a Saturday night, proteins can act differently when crowded together than when they are more spread out.
A team of University researchers is at the forefront of studying this phenomenon as they focus on how water acts between proteins surrounded by bulky molecules, known as crowded proteins. The research may enable scientists to better understand how proteins work, which can lead to improved drug treatments in the future.
The researchers’ paper, “Crowding Induced Collective Hydration of Biological Macromolecules over Extended Distances,” was recently published in the Journal of the American Chemical Society and is accessible online.
Proteins called enzymes carry out many crucial chemical reactions in the body. They are often studied in terms of the molecules they bind to carry out these life-sustaining reactions. However, an aspect of protein chemistry that has been overlooked is that they are almost always acting in crowded, watery environments.
Assistant Chemistry Prof. Kevin Kubarych said crowded environments can alter the way in which we view protein activity.
“When you stuff people together, like kids at a club — as the walls of the club start to get closer and closer together, the music might be the same and the dancing might be similar, but the way that the actual motion of people works through the club is going to change. If you want to go from here to there, you have to mess with 25 people on your way,” Kubarych said.
In the researchers’ model, crowding of proteins causes the water surrounding them to slow down. In keeping with Kubarych’s example, they have less room to move in the club. As a result, the proteins, which normally fluctuate in shape, also begin to slow down.
“If the solute is just protein, that means that proteins are indirectly sharing information with each other through this attribute of water,” Kubarych said.
The information could have important pharmaceutical and medical implications. Each protein has very specific molecules called substrates to which it binds and on which it performs certain actions. For example, the protein salivary amylase, present in human saliva, starts breaking food apart as it’s eaten. Many important drugs work by closely mimicking substrates that proteins would normally bind to, keeping them from binding to their normal substrates and thus causing some change in the body.
Exactly how well proteins bind to their substrates and how quickly this happens depends on a host of factors, one of which may have to do with the state of the water surrounding the protein.
Kubarych said crowding could affect water molecules, which then affects unbound proteins’ fluctuations, changing the way in which they bind to their substrates.
Knowing more about how proteins respond to crowding could illuminate more about the speed at which they bind to certain drugs, which can be the difference between life and death in some cases.
“Waiting for one or two days for your drug to take effect — that’s only a factor of two in chemistry but can make a huge difference for a sick person,” Kubarych said.