Life owes a lot to origami. Seriously. It’s all about the fold. As with the ancient Japanese paper art form, newly synthesized proteins bend back on themselves to become functional, three-dimensional structures.
If the bends go as they should, the protein becomes what it is meant to become and ultimately a crane or other creature results. If not, the end product is an aggregated wad of worthless protein that can cause a malformed or diseased creature. Mis-folded proteins, for instance, have been linked to such neurodegenerative diseases as mad-cow, Parkinson’s and Alzheimer’s, as well as emphysema, cystic fibrosis, juvenile cataracts and cancer.
Some recent ground-breaking research by Notre Dame’s Patricia Clark and a colleague from the Massachusetts Institute of Technology offers new insight into this disease-causing process. Clark, who is the John Cardinal O’Hara, CSC, associate professor of chemistry and biochemistry, and Bonnie Berger, a mathematician from MIT, developed an algorithm that accurately predicts which portions of a protein will inhibit the mis-folding that leads to protein aggregation. The ND chemist conducted experimental work, while the MIT mathematician tested computational predictions based on Clark’s results.
Clark and Berger discovered experimentally and mathematically that the key to aggregation-resistant proteins is a chemical “capping structure” which occurs at the end of a properly folded protein sequence. The cap prevents the protein from doubling back on itself, interacting with copies of itself. If the cap is chemically removed, Clark found the protein quickly mis-folds and aggregates.
“It was really exciting when we found that Bonnie’s mathematical predictions held water in our experiments,” Clark says. “It means we are that much closer to figuring out what these mis-folded structures look like, and therefore how we might be able to prevent them from forming.”
John Monczunski is an associate editor of Notre Dame Magazine.