The accumulation of misfolded porins in the periplasm of bacteria triggers a proteolytic cascade, initiated by activation of DegS, a member of the family of HtrA proteases. Activation of DegS ultimately leads to the expression of genes encoding the periplasmic protein folding machinery. A new study now reveals that binding of exposed C-termini of unassembled porins to the PDZ domain of DegS induces structural rearrangements that activate the catalytic site of the protease domain.