Some proteins help other proteins fold into their normal shapes. We study how these types of proteins act in the reproduction of prions—infectious, misfolded proteins. This protein misfolding problem is related to a similar occurrence seen in many human diseases.
Before a protein can do its work, it folds into a 3-dimensional shape. Although most proteins fold into this shape on their own, some require the help of other molecules to fold properly. These proteins, called chaperones, guide newly made molecules into their correct shape. Mutations in chaperones strongly influence how misfolded proteins make cells sick.
We use genetics, molecular biology, and biochemistry to study prions of yeast cells to understand how chaperones modify the growth of fibrous masses called amyloids. Amyloid masses form toxic deposits connected with the death of tissue in many human disorders, including type 2 diabetes and Alzheimer’s disease.
Our studies suggest that chaperones increase amyloid masses by breaking fibers into many pieces. Each of these pieces continue to help the amyloid structure grow. These prion “seeds” must also replicate to survive in the growing yeast population. Our studies of mutations in various chaperones reveal the molecular interactions that influence seed replication.