Sometimes, science happens in a eureka moment. For Art Horwich, a molecular biologist at Yale University, the idea that the cell has foldases that assist folding of polypeptides to the native state came at 11:00 p.m. on a September night in 1987 when Horwich and his student Ming Cheng were chatting about a yeast mutant library. Horwich asked: "'What if there is a machinery inside mitochondria that actually helps imported proteins to fold to their native form?'" Yes, it was outlandish, but they already had the strains to see whether such a machine might exist.
Within days, Cheng produced this immunoblot, which examined a set of yeast mutant strains that produced the mitochondrial protein ornithine transcarbamylase (OTC) but did not contain any enzyme activity. A particular strain, alpha143 (red arrow), had made a mature-sized subunit. The subunit had apparently gotten into the mitochondria, since its signal peptide had been cleaved ...
