A genetically incorporated crosslinker reveals chaperone cooperation in acid resistance

In this article, Chen et al. developed photocrosslinking amino acid strategy to better understand the function of the protein, HdeA. HdeA is a protein naturally found in enteric bacteria, and is believed to be a chaperone that allows bacteria to survive in low pH environments like the mammalian stomach. However, how HdeA does this was previously unknown. By developing a longer and more flexible photocrosslinker, Chen et al. were able to deduce important protein-protein interactions. It was found that HdeA interacts with periplasmic chaperones at a low pH. This interaction is believed to protect the periplasmic chaperones from denaturation in an acidic environment, and once in a neutral environment, the periplasmic chaperones can enhance the refolding of other proteins.