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

TitleThe sacrificial adaptor protein Skp functions to remove stalled substrates from the β-barrel assembly machine.
Publication TypeJournal Article
Year of Publication2022
AuthorsCombs, AN, Silhavy, TJ
JournalProc Natl Acad Sci U S A
Volume119
Issue1
Date Published2022/01/04
ISSN1091-6490
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.

DOI10.1073/pnas.2114997119
Alternate JournalProc Natl Acad Sci U S A
PubMed ID34969846