Crystal structure of DegP (HtrA) reveals a new protease-chaperone machine

Nature. 2002 Mar 28;416(6879):455-9. doi: 10.1038/416455a.


Molecular chaperones and proteases monitor the folded state of other proteins. In addition to recognizing non-native conformations, these quality control factors distinguish substrates that can be refolded from those that need to be degraded. To investigate the molecular basis of this process, we have solved the crystal structure of DegP (also known as HtrA), a widely conserved heat shock protein that combines refolding and proteolytic activities. The DegP hexamer is formed by staggered association of trimeric rings. The proteolytic sites are located in a central cavity that is only accessible laterally. The mobile side-walls are constructed by twelve PDZ domains, which mediate the opening and closing of the particle and probably the initial binding of substrate. The inner cavity is lined by several hydrophobic patches that may act as docking sites for unfolded polypeptides. In the chaperone conformation, the protease domain of DegP exists in an inactive state, in which substrate binding in addition to catalysis is abolished.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Crystallography, X-Ray
  • Escherichia coli
  • Heat-Shock Proteins*
  • Models, Molecular
  • Molecular Chaperones / chemistry*
  • Periplasmic Proteins*
  • Protein Conformation
  • Protein Structure, Tertiary
  • Recombinant Proteins / chemistry
  • Serine Endopeptidases / chemistry*


  • Heat-Shock Proteins
  • Molecular Chaperones
  • Periplasmic Proteins
  • Recombinant Proteins
  • DegP protease
  • Serine Endopeptidases

Associated data

  • PDB/1KY9