Deanna Csomo McCool | October 15, 2017
Determining how proteins function on a molecular level is crucial to understanding the underlying basis for disease. Now scientists at the University of Notre Dame are one step closer to unraveling the mystery of how intrinsically disordered proteins work, according to new research published in Science.
Proteins are chains of amino acids that fold into three-dimensional structures, giving them their shape and determining the way they interact with other molecules. Many proteins form rigid structures, but intrinsically disordered proteins (IDPs) are “floppy” and do not fold into a regular structure. These disordered proteins are floppy because their parts interact just as well with water as with each other. Up to 30 percent of all proteins are disordered — and must be disordered in order to work properly.
Researchers have struggled to understand precisely how disordered IDPs are — and how they work. Their floppy structures make it difficult to extract their exact dimensions, making the extent of that disorder, along with the strengths of the interactions, unclear. These details are crucial to understanding how IDPs carry out their necessary functions in cells.
“We have excellent methods available for determining the structures of proteins that fold into one rigid structure, but a significant fraction of all proteins are too flexible to be studied using these methods. Even worse, results from two of the most commonly used methods to study IDPs disagree with each other,” said Patricia Clark, a biophysicist at Notre Dame and co-author of the study. “So we developed a novel analysis procedure to help resolve this.”