Review Protein quality control in the bacterial periplasm

The proper functioning of extracytoplasmic proteins requires their export to, and productive folding in, the correct cellular compartment. All proteins in Escherichia coli are initially synthesized in the cytoplasm, then follow a pathway that depends upon their ultimate cellular destination. Many proteins destined for the periplasm are synthesized as precursors carrying an N-terminal signal sequence that directs them to the general secretion machinery at the inner membrane. After translocation and signal sequence cleavage, the newly exported mature proteins are folded and assembled in the periplasm. Maintaining quality control over these processes depends on chaperones, folding catalysts, and proteases. This article summarizes the general principles which control protein folding in the bacterial periplasm by focusing on the periplasmic maltose-binding protein. Review Although all the information necessary for a protein to reach a native structure is contained in its amino acid sequence, in vivo protein folding requires the participation of protein factors; molecular chaperones, folding catalysts and proteases, that monitor or regulate this process through many cellular functions. Under physiological conditions, these factors maintain quality control of protein biosynthesis, and errors or failures of the protein folding process are rare. However, incorrectly folded or misfolded proteins can appear as a result of (i) spontaneous or inducible mutations that affect protein folding pathways, (ii) exposure of the cell to environmental stress, such as elevated temperatures or hyperosmolarity, and (iii) overexpression of recombinant genes. In these cases, the polypeptide chain, instead of folding into the native biologically active state, misfolds, and eventually induces a stress response [1]. The resulting misfolded proteins may either be degraded by proteases, repaired by chaperones, or aggregated and sequestered as inclusion bodies (IBs), when escaping protein folding quality control [2]. In the cytoplasm of Escherichia coli, this control is performed mainly by a set of stress-inducible chaperones and proteases collectively known as heat shock proteins (Hsps). The presence of cellular membrane-bounded compartments in E. coli further complicates these issues of protein biosynthesis, and implies the existence of distinct folding and degradation machineries, quality control systems, for extracytoplasmic proteins [3]. The bacterial periplasm is separated from the extracellular milieu only by the porous outer membrane, and hence is more susceptible to changes in the environment than the cytoplasm. Thus, protein quality control in the periplasm is crucial for the survival of bacterial cells. Here we summarize the main features of protein folding in the periplasm of E. coli, and focus on studies using a model system, the maltosebinding protein. Biosynthesis of periplasmic proteins In E. coli, exported proteins with an ultimate destination of the periplasm and outer membrane are synthesized as precursors with a cleavable amino-terminal signal Published: 07 May 2004 Microbial Cell Factories 2004, 3:4 Received: 18 March 2004 Accepted: 07 May 2004 This article is available from: http://www.microbialcellfactories.com/content/3/1/4 © 2004 Miot and Betton; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.