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

Nature volume 416, pages 455–459 (2002)Cite this article

A Corrigendum to this article was published on 02 May 2002

Abstract

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 degraded1. 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 activities2. 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.

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Figure 1: Structure of DegP.
Figure 2: Peptide-binding sites of PDZ1 and PDZ2.
Figure 3: The protease domain.
Figure 4: The central cavity.

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Acknowledgements

We thank C. Spiess for providing cells for SeMet expression, and G. P. Bourenkov and J. McCarthy for assistance during data collection at beamlines BW6 (DESY, Hamburg) and ID14-4 (ESRF, Grenoble), respectively. We thank R. A. John and W. Bode for critical reading of the manuscript. Financial support by EU ERB (M.G.-F.), DFG (R.H.) and Aventis (T.C.) is acknowledged.

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Authors and Affiliations

  1. Max-Planck-Institut für Biochemie, Abteilung Strukturforschung, Am Klopferspitz 18A, Martinsried, 82152, Germany

    Tobias Krojer, Marta Garrido-Franco, Robert Huber & Tim Clausen

  2. Cardiff University, School of Biosciences, Museum Avenue, Cardiff, CF10 3US, UK

    Tobias Krojer & Michael Ehrmann

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  1. Tobias Krojer
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Correspondence to Tim Clausen.

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Krojer, T., Garrido-Franco, M., Huber, R. et al. Crystal structure of DegP (HtrA) reveals a new protease-chaperone machine. Nature 416, 455–459 (2002). https://doi.org/10.1038/416455a

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