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Biochemistry

pH-tunable protein conformation switch

Histidine residues change how a protein folds

by Laura Howes
May 18, 2019 | APPEARED IN VOLUME 97, ISSUE 20

 

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Credit: David Baker
At low pH, the protonated histidine side chain disrupts hydrogen bonding and causes a change in conformation.

Naturally occurring proteins often change their shape, or conformation, as their environment changes. This property is key to the way they do their jobs in biology. But designing similar switches in the lab has been a challenge: change one interaction and it might have unintended consequences somewhere else in the protein. At the University of Washington, David Baker’s lab has long been designing protein folds and systems from scratch using Baker’s Rosetta software. The group now uses its expertise to switch protein conformation with a change in pH (Science 2019, DOI: 10.1126/science.aav7897). The team’s new α-helical proteins contain a network of hydrogen bonds, many of which involve histidine residues. As the pH decreases, the histidine side chains are protonated and the hydrogen bonding network is disrupted, causing the proteins to adjust their shape. By adjusting the network and the surrounding sequences, the group can make proteins that penetrate cell membranes and change conformation at various pH values, characteristics that could be useful for drug delivery.

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