A team of researchers at the University of Massachusetts Amherst has announced a major new advance in understanding how our genetic information eventually translates into functional proteins — one of the building blocks of human life. The research, recently published in the Proceedings of the National Academy of Sciences (PNAS), elucidates how chaperones display “selective promiscuity” for the specific proteins — their “clients” — they serve. This property enables them to play an essential role in maintaining healthy cells and is a step forward in understanding the origins of a host of human illnesses, from cancer to ALS.
There are four “letters” in the linear DNA code: A, C, G and T. Through the complex processes of transcription, followed by protein synthesis and finally protein folding, those four, two-dimensional letters turn into a 20-letter, three-dimensional recipe for proteins. Most of the time, this process works flawlessly, and our cells can build and reproduce themselves smoothly. But when something goes awry, the results can be catastrophic. Luckily, cells rely on a rigorous quality control to offset the devastating consequences.
The protein folding process, during which a chain of amino acids assumes its final shape as a protein, can be especially fraught. Researchers have long known that special molecules called chaperones help shepherd the protein into its final, correct shape. These “chaperones” can figure out which proteins are at risk of being deformed and can then lend that protein additional help. But how exactly they do their work has been poorly understood: “The chaperones do some kind of magic,” says Alexandra Pozhidaeva, co-lead author of the paper who contributed to this study as a postdoctoral research associate at UMass Amherst and is currently a postdoctoral fellow at UConn Health. “What we’ve done is to reveal the mechanics behind the trick.”
The trick is that, though there are tens of thousands of different proteins in our cells, each with a different shape and function, there are far fewer chaperones. “How is it,” asks Lila Gierasch, Distinguished Professor of biochemistry and molecular biology at UMass Amherst and the paper’s senior author, “that the same chaperones can help many different proteins?” The answer lies in what the authors call the chaperones’ “selective promiscuity.”
The team relied on the cutting-edge, in-house resources of UMass