In 1992, Judith Frydman, PhD, discovered a molecular complex with an essential purpose in all of our cells: folding proteins correctly.
The complex, a type of “protein chaperone” known as TRiC, helps fold thousands of human proteins: It was later found that about 10% of all our proteins pass through its barrel structure.
All animals have several different kinds of protein chaperones, each with its own job of helping fold proteins in the cell. TRiC binds to newborn proteins and shapes these strings of amino acids into the correct 3D structures, allowing them to carry out their important functions in the cell.
Frydman, the Donald Kennedy Chair in the School of Humanities and Sciences and a professor of biology and genetics, met Ingo Kurth, MD, a pediatrician at the RWTH Aachen University, during a recent sabbatical in Germany, who presented her with an interesting conundrum. Three decades after Frydman’s discovery and many more insights into TRiC’s mechanism later, the pediatrician had found a mutation in one of TRiC’s components in a child with intellectual disability, seizures and brain malformations.
Could the TRiC mutation be responsible for the child’s symptoms? Although dysfunctions in the complex are linked to cancer and Alzheimer’s disease, germline mutations -; mutations present in all cells in an organism -; in TRiC had never been implicated in a developmental disease. Because proteins must be folded correctly to function correctly and because TRiC is involved in shaping so many proteins, scientists assumed any mutation that altered TRiC’s ability