Membrane-associated DegP in Bordetella chaperones a repeat-rich secretory protein.

The chaperone/protease DegP belongs to the HtrA superfamily and is involved in protein quality control in the periplasm of Gram-negative bacteria. In Escherichia coli, typical substrates are unfolded or misfolded globular proteins that trigger the rearrangement of inactive DegP hexamers into substrate-sequestering 12- or 24-mers 'cages' for refolding or degradation. In Bordetella pertussis, DegP facilitates, in addition, the secretion of FHA, a long β-helical adhesin that passes through the periplasm in an extended conformation. We show that DegP exists as soluble trimers and as a membrane-associated form. Different substrates interact differently with the distinct forms of DegP, and membrane-associated DegP has high affinity for non-native FHA. Unlike more globular substrates, FHA does not efficiently mediate rearrangement of trimers into proteolytically active, short-lived dodecamers. In contrast to these dodecamers, membrane-associated DegP is not committed to substrate degradation, although it is proteolytically competent. In B. pertussis, membrane-associated DegP thus represents a specific functional form serving as a holding chaperone for client proteins including FHA. If FHA secretion is impaired, membrane-associated DegP participates in its degradation. This form of DegP is appropriate to handle substrates unsuitable to be sequestered in cages or non-folded, secretory proteins that must not be degraded. [ABSTRACT FROM AUTHOR]