The Escherichia coli DjlA and CbpA Proteins Can Substitute for DnaJ in DnaK-Mediated Protein Disaggregation

Abstract

The DnaJ (Hsp40) protein of Escherichia coli serves as a cochaperone of DnaK (Hsp70), whose activity is involved in protein folding, protein targeting for degradation, and rescue of proteins from aggregates. Two other E. coli proteins, CbpA and DjlA, which exhibit homology with DnaJ, are known to interact with DnaK and to stimulate its chaperone activity. Although it has been shown that in dnaJ mutants both CbpA and DjlA are essential for growth at temperatures above 37°C, their in vivo role is poorly understood. Here we show that in a dnaJ mutant both CbpA and DjlA are required for efficient protein dissaggregation at 42°C.

Genetic Interaction Between theEscherichia coliAcpT Phosphopantetheinyl Transferase and the YejM Inner Membrane Protein

“…Hence, we have asked if the heat-shock regulon is induced upon AcpT overexpression by assaying expression of the classical heat-shock protein, DnaJ, by use of a chromosomal dnaJ-lacZY fusion construct. Construction of the fusion eliminated DnaJ function, but since DnaJ is functionally replaced by either of two other cochaperone proteins, DjlA and CbpA (Gur et al 2004), DnaJ mutants behave normally in regards to heat shock. Use of this fusion provides an assay for DnaK expression since it is encoded by the promoter-proximal gene in the dnaK-dnaJ operon (Cowing et al 1985;Bardwell et al 1986).…”

Complex Regulation of the DnaJ Homolog CbpA by the Global Regulators σ S and Lrp, by the Specific Inhibitor CbpM, and by the Proteolytic Degradation of CbpM

“…Three of the E. coli DnaJ homologs, DnaJ, CbpA, and DjlA, have significant functional overlap, although it is unclear why this redundancy exists (11)(12)(13)27). Conceivably, each homolog may recognize its own specific set of substrates that are preferentially targeted for remodeling by DnaK.…”

Structural Basis of the Regulation of the CbpA Co-chaperone by its Specific Modulator CbpM

“…19 In vitro, the CbpA co-chaperone binds efficiently to protein substrates, 14 activates the DnaK chaperone for the remodelling of protein complexes and promotes protein disaggregation. 18,20 Like DnaJ, CbpA forms a homodimer in solution, with dimerization in both proteins mediated through the C-terminal domain. 18,19 A unique feature of CbpA as compared to DnaJ is its intimate interaction with a specific inhibitory partner protein, CbpM.…”