When E. coli is swallowed, the pH of its environment drops precipitously. The tiny protein HdeA, helps defend the bacteria by activating its chaperone function. HdeA senses acid directly, and partially unfolds. The flexibility gained through partial unfolding allows it to adapt to and bind various damaged proteins, protecting them from aggregation and proteolysis much like plastic wrappers stop hard candies from sticking together. HdeA exploits the energy from extracellular pH changes to facilitate protein folding, HdeA releases its substrate proteins slowly. This keeps the concentration of aggregation-sensitive intermediates below the aggregation threshold, providing a straightforward and ATP-independent mechanism to facilitate protein refolding.
Tapley et. al. (2009) Structural plasticity of an acid-activated chaperone allows promiscuous substrate binding. Proc Natl Acad Sci U S A 106: 5557-5562. (Pubmed)
Tapley T et. al. (2010) Protein refolding by pH-triggered chaperone binding and release. Proc Natl Acad Sci U S A 107: 1071-1076. (Pubmed) was cited as a paper of special interest by Lila Gierasch in Current Opinion in Structural Bioloy2011, 21:32-41