Bowl-shaped oligomeric structures on membranes as DegP's new functional forms in protein quality control

Proc Natl Acad Sci U S A. 2009 Mar 24;106(12):4858-63. doi: 10.1073/pnas.0811780106. Epub 2009 Mar 2.

Abstract

In the periplasm of Escherichia coli, DegP (also known as HtrA), which has both chaperone-like and proteolytic activities, prevents the accumulation of toxic misfolded and unfolded polypeptides. In solution, upon binding to denatured proteins, DegP forms large cage-like structures. Here, we show that DegP forms a range of bowl-shaped structures, independent of substrate proteins, each with a 4-, 5-, or 6-fold symmetry and all with a DegP trimer as the structural unit, on lipid membranes. These membrane-bound DegP assemblies have the capacity to recruit and process substrates in the bowl chamber, and they exhibit higher proteolytic and lower chaperone-like activities than DegP in solution. Our findings imply that DegP might regulate its dual roles during protein quality control, depending on its assembly state in the narrow bacterial envelope.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Membrane / enzymology*
  • Cell Membrane / ultrastructure
  • Escherichia coli / cytology
  • Escherichia coli / enzymology*
  • Escherichia coli / ultrastructure
  • Heat-Shock Proteins / chemistry*
  • Heat-Shock Proteins / ultrastructure
  • Lipids / chemistry
  • Molecular Chaperones / metabolism
  • Periplasmic Proteins / chemistry*
  • Periplasmic Proteins / ultrastructure
  • Protein Processing, Post-Translational
  • Protein Structure, Quaternary
  • Serine Endopeptidases / chemistry*
  • Serine Endopeptidases / ultrastructure
  • Substrate Specificity

Substances

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