De novo design of tunable, pH-driven conformational changes

Designed to respond Protein design has achieved success in finding sequences that fold to very stable target structures. Protein function, however, often requires conformational dynamics. Boyken et al. describe designed proteins that undergo conformational transitions in response to pH. They designed helical oligomers in which histidines are positioned in hydrogen-bond networks at the interfaces, with complimentary hydrophobic packing around the networks. Lowering the pH protonated the histidine, disrupting the oligomers. After endocytosis into low-pH compartments in cells, the designed proteins disrupted endosomal membranes. Science , this issue p. 658