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Cited by 61Heat shock proteins researchProtein Structure and DynamicsAdvanced Electron Microscopy Techniques and Applications

Newly folded substrates inside the molecular cage of the HtrA chaperone DegQ

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Malet, Hélène, Canellas, Flavia, Sawa, Justyna, Yan, Jun, Thalassinos, Konstantinos, Ehrmann, Michael, Clausen, Tim, Saibil, Helen R·2012·Nature Structural & Molecular Biology
DOI 10.1038/nsmb.2210PMC PMC3272482
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Abstract

The HtrA protein family combines chaperone and protease activities and is essential for protein quality control in many organisms. Whereas the mechanisms underlying the proteolytic function of HtrA proteins are well characterized, their chaperone activity remains poorly understood. Here we describe cryo-EM structures of Escherichia coli DegQ in its 12- and 24-mer states in complex with model substrates, providing a structural model of HtrA chaperone action. Up to six lysozyme substrates bind inside the DegQ 12-mer cage and are visualized in a close-to-native state. An asymmetric reconstruction reveals the binding of a well-ordered lysozyme to four DegQ protomers. DegQ PDZ domains are located adjacent to substrate density and their presence is required for chaperone activity. The substrate-interacting regions appear conserved in 12- and 24-mer cages, suggesting a common mechanism of chaperone function.

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  • DEGP and DEGQ play a central role in protein quality control in the bacterial periplasmic space, through degrading denatured and misfolded proteins accumulated under adverse conditions.

    “As HSP homologous proteases, DEGP and DEGQ were found to play a central role in protein quality control in the bacterial periplasmic space, through degrading denatured and misfolded proteins accumulated under adverse conditions.55,56”

    From Identification of heptapeptides targeting a lethal bacterial strain in septic mice through an integrative approach (2022) · cites this paper as [56]

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Authors
Malet, H., Canellas, F., Sawa, J., Yan, J., Thalassinos, K., Ehrmann, M., Clausen, T., & Saibil, H. R.
Affiliations
  • Institute of Structural and Molecular Biology (GB)
  • Research Institute of Molecular Pathology (AT)
  • University of Duisburg-Essen (DE)
Corresponding author
Saibil, Helen R
ORCID
Venue
Nature Structural & Molecular Biology
Publisher
Springer Science and Business Media LLC
Published
2012-01-15
Volume
19
Issue
2
Pages
152-157
ISSN
  • 1545-9985 (ISSN-L)
  • 1545-9993
DOI
10.1038/nsmb.2210
PMC
PMC3272482
OpenAlex
W2022648483
Cited by
61
References
1
Citations by year
2026: 2 · 2025: 2 · 2024: 3 · 2023: 3 · 2022: 2 · 2021: 6 · 2020: 5 · 2019: 3 · 2018: 6 · 2017: 4 · 2016: 4 · 2015: 6 · 2014: 4 · 2013: 7 · 2012: 4
FWCI
2.70
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Structural & Molecular Biology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • BIROn (Birkbeck, University of London) (submittedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
Funders
  • Wellcome Trust (079605, 089050)
  • Biotechnology and Biological Sciences Research Council (BB/F010281/1)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Advanced Electron Microscopy Techniques and Applications
Keywords
DegQ, protein folding, substrate binding, PDZ domain, lysozyme, Escherichia coli, protein quality control, HtrA protease, cryo-EM structure
MeSH terms
Escherichia coli, Models, Molecular, Muramidase, Serine Endopeptidases, Molecular Chaperones, Cryoelectron Microscopy, Protein Structure, Quaternary, Escherichia coli Proteins, Protein Multimerization

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