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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    • "Whether the differential localization of this enzyme affects its function and/or substrate selectivity remains to be demonstrated. Membrane-associated proteases are central in cell physiology as they perform quality control of membrane proteins and are involved in processing of exported polypeptides, regulatory circuits, cell-signaling, the stress response as well as the assembly of cell surface structures [13]. Most of the membrane proteases that occur in bacteria and eukaryotes are also encoded in archaeal genomes, except for the ATP-dependent metallo protease FtsH [2] [7]. "
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    ABSTRACT: This data article provides information in support of the research article "Global role of the membrane protease LonB in Archaea: Potential protease targets revealed by quantitative proteome analysis of a lonB mutant in Haloferax volcanii" [1]. The proteome composition of a wt and a LonB protease mutant strain (suboptimal expression) in the archaeon Haloferax volcanii was assessed by a quantitative shotgun proteomic approach. Membrane and cytosol fractions of H. volcanii strains were examined at two different growth stages (exponential and stationary phase). Data is supplied in the present article. This study represents the first proteome examination of a Lon-deficient cell of the Archaea Domain.
    Full-text · Article · Mar 2015 · Journal of proteomics
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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.
    Preview · Article · Nov 2013 · Biochimica et Biophysica Acta
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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.
    Full-text · Article · Apr 2013 · Molecular Microbiology
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