The sacrificial adaptor protein Skp functions to remove stalled substrates from the β-barrel assembly machine

Ashton N. Combs, Thomas J. Silhavy

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

The biogenesis of integral β-barrel outer membrane proteins (OMPs) in gram-negative bacteria requires transport by molecular chaperones across the aqueous periplasmic space. Owing in part to the extensive functional redundancy within the periplasmic chaperone network, specific roles for molecular chaperones in OMP quality control and assembly have remained largely elusive. Here, by deliberately perturbing the OMP assembly process through use of multiple folding-defective substrates, we have identified a role for the periplasmic chaperone Skp in ensuring efficient folding of OMPs by the β-barrel assembly machine (Bam) complex. We find that β-barrel substrates that fail to integrate into the membrane in a timely manner are removed from the Bam complex by Skp, thereby allowing for clearance of stalled Bam–OMP complexes. Following the displacement of OMPs from the assembly machinery, Skp subsequently serves as a sacrificial adaptor protein to directly facilitate the degradation of defective OMP substrates by the periplasmic protease DegP. We conclude that Skp acts to ensure efficient β-barrel folding by directly mediating the displacement and degradation of assembly-compromised OMP substrates from the Bam complex.

Original languageEnglish (US)
Article numbere2114997119
JournalProceedings of the National Academy of Sciences of the United States of America
Volume119
Issue number1
DOIs
StatePublished - Jan 4 2022

All Science Journal Classification (ASJC) codes

  • General

Keywords

  • Bam complex
  • Outer membrane protein biogenesis
  • Periplasmic chaperones
  • β-barrel

Fingerprint

Dive into the research topics of 'The sacrificial adaptor protein Skp functions to remove stalled substrates from the β-barrel assembly machine'. Together they form a unique fingerprint.

Cite this