By Tom McBrien, Daily Staff Reporter
Published March 18, 2014
Billions of years ago, organic molecules dissolved in the Earth’s oceans combined to create the first bacterial life — the common ancestor of all living things. While the exact mechanism that sparked this life is unknown, University researchers have confirmed a new function for an ancient molecule that may be a part of the puzzle.
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In a recently published paper titled “Polyphosphate Is a Primordial Chaperone,” researchers from Biology Prof. Ursula Jakob’s lab explain how a molecule called inorganic polyphosphate can act as a chaperone, meaning it helps proteins to fold into the complex 3-D shapes that dictate their functions.
Proteins are crucial to the development of life, but the process by which they were first created and maintained in cells is an interesting riddle for scientists. Most proteins rely on other proteins, called chaperones, to fold them into shape so that they can work. But these chaperone proteins require the proteins they fold for their own synthesis.
Chaperones are also important for the maintenance of healthy proteins. When exposed to stressors such as high temperature or harsh chemicals, proteins may unfold in a process called denaturing and are rendered useless — a major problem for the body. Diseases like sickle cell anemia, Alzheimer’s and Parkinson’s all result from misfolded proteins.
LSA senior Nico Wagner, a co-author of the paper, said inorganic polyphosphate’s simple, non-proteinaceous nature is an important characteristic that may answer this riddle.
“We think that it’s unlikely that the first proteins just folded without any help, they had something to help them and that something had to be simple because it couldn’t be another protein, or else you would have a chicken-or-egg question,” he said.
Inorganic polyphosphate, also known as polyP, is made up of a long chain of phosphate molecules, which are common in the cell. The fact that it may act as a chaperone while not being a protein, in addition to its demonstrated ancient origins, makes it a tempting candidate for a crucial molecule in the development of life.
Jakob said the research interest came from an observation made by researchers in the lab: when cells were exposed to stress, they became starved for ATP, the high-energy molecule needed to create polyP.
Further experiments compared bacteria that were able to produce polyP to bacteria that couldn’t, and examined proteins in solutions exposed to polyP with proteins not exposed to polyP. The results showed that proteins exposed to polyP reacted to stress much better than proteins that were not exposed, which quickly unfolded and became useless.
Based on these results, the researchers are confident that polyP acts as an important chaperone-protein replacement. It has been found in all of the organisms in which it has been tested for, and is believed to exist in all forms of life, pointing to its evolutionary significance.
Wagner said the next step is to figure out how exactly polyP works to protect proteins. Jakob emphasized that this could have clinical consequences for diseases resulting from misfolded proteins. Further understanding of protein folding and the molecules involved could potentially lead to insights in treating these diseases.