Membrane Proteases in the Bacterial Protein Secretion and Quality Control Pathway

Department of Chemistry, The Ohio State University, Columbus, Ohio, USA.
Microbiology and molecular biology reviews: MMBR (Impact Factor: 14.61). 06/2012; 76(2):311-30. DOI: 10.1128/MMBR.05019-11
Source: PubMed


Proteolytic cleavage of proteins that are permanently or transiently associated with the cytoplasmic membrane is crucially important for a wide range of essential processes in bacteria. This applies in particular to the secretion of proteins and to membrane protein quality control. Major progress has been made in elucidating the structure-function relationships of many of the responsible membrane proteases, including signal peptidases, signal peptide hydrolases, FtsH, the rhomboid protease GlpG, and the site 1 protease DegS. These enzymes employ very different mechanisms to cleave substrates at the cytoplasmic and extracytoplasmic membrane surfaces or within the plane of the membrane. This review highlights the different ways that bacterial membrane proteases degrade their substrates, with special emphasis on catalytic mechanisms and substrate delivery to the respective active sites.

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Available from: Ross E Dalbey, Mar 03, 2015
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    • "Folding of soluble cytoplasmic domains of membrane proteins might be supported by cytoplasmic chaperones such as DnaK, whereas that of periplasmic domains of membrane proteins might be supported by periplasmic chaperones such as DegP (which can also act as a protease). The FtsH complex is involved in quality control and degradation of membrane proteins [22] [23]. "
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    ABSTRACT: Escherichia coli is by far the most widely used bacterial host for the production of membrane proteins. Usually, different strains, culture conditions and production regimes are screened for to design the optimal production process. However, these E. coli-based screening approaches often do not result in satisfactory membrane protein production yields. Recently, it has been shown that (i) E. coli strains with strongly improved membrane protein production characteristics can be engineered or selected for, (ii) many membrane proteins can be efficiently produced in E. coli-based cell-free systems, (iii) bacteria other than E. coli can be used for the efficient production of membrane proteins, and, (iv) membrane protein variants that retain functionality but are produced at higher yields than the wild-type protein can be engineered or selected for. This article is part of a Special Issue entitled:Protein trafficking & Secretion.
    Biochimica et Biophysica Acta 11/2013; 1843(8). DOI:10.1016/j.bbamcr.2013.10.023 · 4.66 Impact Factor
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    • "DegP and DegQ are synthesized initially with N-terminal signal peptides. After transport from the cytosol across the inner membrane via the Sec translocation pathway, they are released into the periplasm upon signal peptide cleavage, where they function in their characteristic roles (Lipinska et al., 1990; Waller and Sauer, 1996; Dalbey et al., 2012). HtrABb first drew our interest when it was found to be a constituent of B. burgdorferi vesicles (Toledo et al., 2012). "
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    ABSTRACT: Borrelia burgdorferi, the spirochaetal agent of Lyme disease, codes for a single HtrA protein, HtrABb (BB0104) that is homologous to DegP of Escherichia coli (41% amino acid identity). HtrABb shows physical and biochemical similarities to DegP in that it has the trimer as its fundamental unit and can degrade casein via its catalytic serine. Recombinant HtrABb exhibits proteolytic activity in vitro, while a mutant (HtrABbS198A) does not. However, HtrABb and DegP have some important differences as well. Native HtrABb occurs in both membrane-bound and soluble forms. Despite its homology to DegP, HtrABb could not complement an E. coli DegP deletion mutant. Late stage Lyme disease patients, as well as infected mice and rabbits developed a robust antibody response to HtrABb, indicating that it is a B-cell antigen. In co-immunoprecipitation studies, a number of potential binding partners for HtrABb were identified, as well as two specific proteolytic substrates, basic membrane protein D (BmpD/BB0385) and chemotaxis signal transduction phosphatase CheX (BB0671). HtrABb may function in regulating outer membrane lipoproteins and in modulating the chemotactic response of B. burgdorferi.
    Molecular Microbiology 04/2013; 88(3). DOI:10.1111/mmi.12213 · 4.42 Impact Factor
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    • "This regulon is induced in response to cell envelope stress caused by antibiotics, alkaline shock and salt shock [8], [9], [18], [31], [38], [39], [43], [48]. The anti-sigma factor of σW, RsiW, is cleaved by the site-1 protease PrsW and the site-2 protease RasP [12], [15], [21], [42], [49]. Consistent with the requirement of PrsW for RsiW degradation, prsW mutant cells have a phenotype that is very similar to the phenotype of sigW mutant cells. "
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    ABSTRACT: Bacteria employ extracytoplasmic function (ECF) sigma factors for their responses to environmental stresses. Despite intensive research, the molecular dissection of ECF sigma factor regulons has remained a major challenge due to overlaps in the ECF sigma factor-regulated genes and the stimuli that activate the different ECF sigma factors. Here we have employed tiling arrays to single out the ECF σ(W) regulon of the Gram-positive bacterium Bacillus subtilis from the overlapping ECF σ(X), σ(Y), and σ(M) regulons. For this purpose, we profiled the transcriptome of a B. subtilis sigW mutant under non-stress conditions to select candidate genes that are strictly σ(W)-regulated. Under these conditions, σ(W) exhibits a basal level of activity. Subsequently, we verified the σ(W)-dependency of candidate genes by comparing their transcript profiles to transcriptome data obtained with the parental B. subtilis strain 168 grown under 104 different conditions, including relevant stress conditions, such as salt shock. In addition, we investigated the transcriptomes of rasP or prsW mutant strains that lack the proteases involved in the degradation of the σ(W) anti-sigma factor RsiW and subsequent activation of the σ(W)-regulon. Taken together, our studies identify 89 genes as being strictly σ(W)-regulated, including several genes for non-coding RNAs. The effects of rasP or prsW mutations on the expression of σ(W)-dependent genes were relatively mild, which implies that σ(W)-dependent transcription under non-stress conditions is not strictly related to RasP and PrsW. Lastly, we show that the pleiotropic phenotype of rasP mutant cells, which have defects in competence development, protein secretion and membrane protein production, is not mirrored in the transcript profile of these cells. This implies that RasP is not only important for transcriptional regulation via σ(W), but that this membrane protease also exerts other important post-transcriptional regulatory functions.
    PLoS ONE 11/2012; 7(11):e48471. DOI:10.1371/journal.pone.0048471 · 3.23 Impact Factor
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