With Arthur L. Horwich, of Yale University and the Howard Hughes Medical Institute.
Proteins are made from chains of 20 different amino acids, each protein with a characteristic sequence. A newly made chain folds in intricate ways into a unique three-dimensional structure that has a biological activity. This folding process was long thought to be a spontaneous process. In the late 1950s, American biochemist Christian Anfinsen showed an enzyme unfolded by treatment with a denaturant spontaneously refolded back to its native form. Work of recent times, however, makes clear that many proteins require additional assistance by specialized proteins, called molecular chaperones, to reach their native active forms. As suggested by their name, molecular chaperones prevent “illicit” interactions between proteins. Such interactions often have deleterious or fatal consequences for the cell or organism, as occurs, for example, in a number of neurodegenerative diseases, including Alzheimer’s and Parkinson’s Diseases. Our work has focused, using a variety of techniques, on one type of chaperone, called a chaperonin, a double-ring “machine” that has the remarkable ability to promote proper folding of an initially captured protein to its native state inside an encapsulated chamber.
