Protein folding and degradation in bacteria:¶To degrade or not to degrade? That is the question

Abstract

In Escherichia coli protein quality control is carried out by a protein network, comprising chaperones and proteases. Central to this network are two protein families, the AAA+ and the Hsp70 family. The major Hsp70 chaperone. DnaK, efficiently prevents protein aggregation and supports the refolding of damaged proteins. In a special case, DnaK, together with the assistance of the AAA+ protein ClpB, can also refold aggregated proteins. Other Hsp70 systems have more specialized functions in the cell, for instance HscA appears to be involved in the assembly of Fe/S proteins. In contrast to ClpB, many AAA+ proteins associate with a peptidase to form proteolytic machines which remove irreversibly damaged proteins from the cellular pool. The AAA+ component of these proteolytic machines drives protein degradation. They are required not only for recognition of the substrate but also for substrate unfolding and translocation into the proteolytic chamber. In many cases, specific adaptor proteins modify the substrate binding properties of AAA+ proteins. While chaperones and proteases do not appear to directly cooperate with each other, both systems appear to be necessary for proper functioning of the cell and can, at least in part, substitute for one another.

Protein aggregation in bacteria: the thin boundary between functionality and toxicity

“…The latter implies spatial compartmentalization of cellular quality control and misfolded proteins into inclusions, which helps the cell to cope with the overload of misfolded proteins and regulate their inheritance. In bacteria the aggregated and misfolded proteins were shown to move to the poles of the cell, forming IBs that function as a temporary zone for cellular detoxification (Dougan et al, 2002;Steffan et al, 2000). The sequestration points towards evolutionary pressure against the inheritance of aggregates to progeny because IBs distribute asymmetrically during cell division and accumulate in the daughter cell harbouring the older poles (Lindner et al, 2008).…”

Global transcriptional response to vancomycin in Mycobacterium tuberculosis

“…hspX has been proposed to play an active role in slowing the growth of M. tuberculosis in vivo immediately following infection. Other chaperone-encoding induced genes were dnaK, grpE, dnaJI, groEL1, groEL2, groES and clpB, whose protein products have been shown to interact with each other in order to prevent protein aggregation and support the refolding of damaged proteins (Dougan et al, 2002). Only one gene involved in protein degradation was induced: Rv2115c (mpa); this gene encodes an AAA ATPase forming ring-shaped complexes homologous to those found in proteasome caps of eukaryotes and was shown to have a role in oxidative stress response and in virulence .…”

The linker-loop region ofEscherichia colichaperone Hsp31 functions as a gate that modulates high-affinity substrate binding at elevated temperatures

“…In the case of DnaK, precise control of binding and release events by two protein cofactors (DnaJ and GrpE) and adenosine nucleotides may be necessary for the chaperone to properly perform its multiple cellular functions, which range from de novo folding at physiological temperatures to protein disaggregation (20). Similarly, because it is an essential folding modulator at all temperatures (21), GroEL requires GroES and ATP-modulated conformational changes to efficiently promote substrate refolding at infinite dilution within its Anfinsen's cage (1).…”