The DsbA signal sequence directs efficient, cotranslational export of passenger proteins to the Escherichia coli periplasm via the signal recognition particle pathway

J Bacteriol. 2003 Oct;185(19):5706-13. doi: 10.1128/JB.185.19.5706-5713.2003.

Abstract

The Escherichia coli cytoplasmic protein thioredoxin 1 can be efficiently exported to the periplasmic space by the signal sequence of the DsbA protein (DsbAss) but not by the signal sequence of alkaline phosphatase (PhoA) or maltose binding protein (MBP). Using mutations of the signal recognition particle (SRP) pathway, we found that DsbAss directs thioredoxin 1 to the SRP export pathway. When DsbAss is fused to MBP, MBP also is directed to the SRP pathway. We show directly that the DsbAss-promoted export of MBP is largely cotranslational, in contrast to the mode of MBP export when the native signal sequence is utilized. However, both the export of thioredoxin 1 by DsbAss and the export of DsbA itself are quite sensitive to even the slight inhibition of SecA. These results suggest that SecA may be essential for both the slow posttranslational pathway and the SRP-dependent cotranslational pathway. Finally, probably because of its rapid folding in the cytoplasm, thioredoxin provides, along with gene fusion approaches, a sensitive assay system for signal sequences that utilize the SRP pathway.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphatases / metabolism
  • Alkaline Phosphatase / chemistry
  • Bacterial Proteins*
  • Carrier Proteins / chemistry
  • Escherichia coli / genetics
  • Escherichia coli / metabolism*
  • Escherichia coli Proteins / metabolism
  • Maltose-Binding Proteins
  • Membrane Transport Proteins / metabolism
  • Periplasm / metabolism
  • Protein Biosynthesis*
  • Protein Disulfide-Isomerases / chemistry*
  • Protein Sorting Signals* / genetics
  • Protein Sorting Signals* / physiology
  • Protein Transport
  • SEC Translocation Channels
  • SecA Proteins
  • Signal Recognition Particle / genetics
  • Signal Recognition Particle / metabolism*
  • Thioredoxins / genetics
  • Thioredoxins / metabolism*

Substances

  • Bacterial Proteins
  • Carrier Proteins
  • Escherichia coli Proteins
  • Maltose-Binding Proteins
  • Membrane Transport Proteins
  • Protein Sorting Signals
  • SEC Translocation Channels
  • Signal Recognition Particle
  • Thioredoxins
  • Alkaline Phosphatase
  • Adenosine Triphosphatases
  • Protein Disulfide-Isomerases
  • SecA Proteins