RRC ID 35594
Author Narita S, Masui C, Suzuki T, Dohmae N, Akiyama Y.
Title Protease homolog BepA (YfgC) promotes assembly and degradation of β-barrel membrane proteins in Escherichia coli.
Journal Proc. Natl. Acad. Sci. U.S.A.
Abstract Gram-negative bacteria are equipped with quality-control systems for the outer membrane (OM) that sense and cope with defective biogenesis of its components. Accumulation of misfolded outer membrane proteins (OMPs) in Escherichia coli leads to activation of σ(E), an essential alternative σ factor that up-regulates transcription of multiple genes required to preserve OM structure and function. Disruption of bepA (formerly yfgC), a σ(E)-regulated gene encoding a putative periplasmic metalloprotease, sensitizes cells to multiple drugs, suggesting that it may be involved in maintaining OM integrity. However, the specific function of BepA remains unclear. Here, we show that BepA enhances biogenesis of LptD, an essential OMP involved in OM transport and assembly of lipopolysaccharide, by promoting rearrangement of intramolecular disulfide bonds of LptD. In addition, BepA possesses protease activity and is responsible for the degradation of incorrectly folded LptD. In the absence of periplasmic chaperone SurA, BepA also promotes degradation of BamA, the central OMP subunit of the β-barrel assembly machinery (BAM) complex. Interestingly, defective oxidative folding of LptD caused by bepA disruption was partially suppressed by expression of protease-active site mutants of BepA, suggesting that BepA functions independently of its protease activity. We also show that BepA has genetic and physical interaction with components of the BAM complex. These findings raised the possibility that BepA maintains the integrity of OM both by promoting assembly of OMPs and by proteolytically eliminating OMPs when their correct assembly was compromised.
Volume 110(38)
Pages E3612-21
Published 2013-9-17
DOI 10.1073/pnas.1312012110
PII 1312012110
PMID 24003122
PMC PMC3780861
MeSH Bacterial Outer Membrane Proteins / biosynthesis* Bacterial Outer Membrane Proteins / metabolism Escherichia coli Escherichia coli Proteins / biosynthesis* Escherichia coli Proteins / genetics Escherichia coli Proteins / metabolism* Gene Expression Regulation, Bacterial / physiology* Immunoprecipitation Metalloproteases / genetics Metalloproteases / metabolism* Periplasmic Proteins / metabolism Protein Folding Proteolysis Sigma Factor / metabolism*
IF 9.504
Times Cited 11
WOS Category BIOCHEMISTRY & MOLECULAR BIOLOGY
Resource
Prokaryotes E. coli ASKA Keio collection pCP20