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The Sec Pathways and Exportomes of

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  • Authors: Brittany K. Miller1, Katelyn E. Zulauf2, Miriam Braunstein3
  • Editors: William R. Jacobs Jr.4, Helen McShane5, Valerie Mizrahi6, Ian M. Orme7
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Department of Microbiology and Immunology, University of North Carolina – Chapel Hill, Chapel Hill, NC 27599; 2: Department of Microbiology and Immunology, University of North Carolina – Chapel Hill, Chapel Hill, NC 27599; 3: Department of Microbiology and Immunology, University of North Carolina – Chapel Hill, Chapel Hill, NC 27599; 4: Howard Hughes Medical Institute, Albert Einstein School of Medicine, Bronx, NY 10461; 5: University of Oxford, Oxford OX3 7DQ, United Kingdom; 6: University of Cape Town, Rondebosch 7701, South Africa; 7: Colorado State University, Fort Collins, CO 80523
  • Source: microbiolspec April 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TBTB2-0013-2016
  • Received 01 February 2016 Accepted 02 March 2017 Published 07 April 2017
  • Miriam Braunstein, braunste@med.unc.edu
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  • Abstract:

    All bacteria utilize pathways to export proteins from the cytoplasm to the bacterial cell envelope or extracellular space. Many exported proteins function in essential physiological processes or in virulence. Consequently, the responsible protein export pathways are commonly essential and/or are important for pathogenesis. The general Sec protein export pathway is conserved and essential in all bacteria, and it is responsible for most protein export. The energy for Sec export is provided by the SecA ATPase. Mycobacteria and some Gram-positive bacteria have two SecA paralogs: SecA1 and SecA2. SecA1 is essential and works with the canonical Sec pathway to perform the bulk of protein export. The nonessential SecA2 exports a smaller subset of proteins and is required for the virulence of pathogens such as . In this article, we review our current understanding of the mechanism of the SecA1 and SecA2 export pathways and discuss some of their better-studied exported substrates. We focus on proteins with established functions in pathogenesis and proteins that suggest potential roles for SecA1 and SecA2 in dormancy.

  • Citation: Miller B, Zulauf K, Braunstein M. 2017. The Sec Pathways and Exportomes of . Microbiol Spectrum 5(2):TBTB2-0013-2016. doi:10.1128/microbiolspec.TBTB2-0013-2016.

Key Concept Ranking

Bacterial Proteins
0.42894223
Tumor Necrosis Factor alpha
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0.42894223

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/content/journal/microbiolspec/10.1128/microbiolspec.TBTB2-0013-2016
2017-04-07
2017-07-23

Abstract:

All bacteria utilize pathways to export proteins from the cytoplasm to the bacterial cell envelope or extracellular space. Many exported proteins function in essential physiological processes or in virulence. Consequently, the responsible protein export pathways are commonly essential and/or are important for pathogenesis. The general Sec protein export pathway is conserved and essential in all bacteria, and it is responsible for most protein export. The energy for Sec export is provided by the SecA ATPase. Mycobacteria and some Gram-positive bacteria have two SecA paralogs: SecA1 and SecA2. SecA1 is essential and works with the canonical Sec pathway to perform the bulk of protein export. The nonessential SecA2 exports a smaller subset of proteins and is required for the virulence of pathogens such as . In this article, we review our current understanding of the mechanism of the SecA1 and SecA2 export pathways and discuss some of their better-studied exported substrates. We focus on proteins with established functions in pathogenesis and proteins that suggest potential roles for SecA1 and SecA2 in dormancy.

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Figures

Image of FIGURE 1
FIGURE 1

Models of SecA1 and SecA2 export in . SecA1 uses ATP hydrolysis to export preproteins through the SecYEG channel in an unfolded, export-competent state. Sec signal peptides (black rectangle) target preproteins (blue ribbon) for export through SecYEG and are then cleaved by a signal peptidase (SP). SecA2 also uses the SecYEG channel and possibly SecA1 to export its own subset of preproteins (green ribbon). The signal peptide (black rectangle) is indistinguishable from canonical Sec signal peptides. Instead, the mature domain’s propensity for cytoplasmic folding is predicted to confer specificity for SecA2.

Source: microbiolspec April 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TBTB2-0013-2016
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Image of FIGURE 2
FIGURE 2

Solute-binding proteins and Mce proteins are exported by the SecA2 pathway. Two classes of SecA2-dependent substrates are SBPs and Mce proteins. Both SBPs and Mce proteins are involved in solute acquisition. In the case of SBPs this involves import of a solute through an ABC transporter permease using energy provided by ATP hydrolysis. Mce transporters are thought to function in a similar manner as ABC transporters to import a lipid substrate through a YrbE permease in an ATP-dependent manner. Although the diagram of an Mce transporter is speculative, the similarities between these two systems are compelling.

Source: microbiolspec April 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TBTB2-0013-2016
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Image of FIGURE 3
FIGURE 3

Multiple components of Mce transporters are reduced in the cell wall of the Δ mutant. The genome contains four loci encoding putative lipid transporters. The genomic regions encoding Mce1, Mce3, and Mce4 transporters are shown with open reading frames colored for Mce proteins that are reduced in quantitative mass spectrometry studies of the () and () Δ mutant cell wall or cell envelope fractions ( 38 , 70 ). In dark blue and/or green are genes for proteins that are significantly reduced ( < 0.01 for and < 0.05 for ) in the Δ mutant; in light blue are genes for Mce proteins that are reduced in the Δ mutant but did not reach statistical significance.

Source: microbiolspec April 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TBTB2-0013-2016
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Image of FIGURE 4
FIGURE 4

SecA2 export is required for virulence. The SecA2 pathway combats multiple host immune mechanisms of macrophages. SecA2 export of PknG in addition to other unknown effectors prevents phagosome acidification and fusion with degradative lysosomes. Export of SodA and KatG by SecA2 combats harmful reactive oxygen radicals and limits apoptosis. SecA2 also inhibits signaling through MyD88 by unknown mechanisms, resulting in lower levels of the proinflammatory cytokines interleukin-6 and tumor necrosis factor alpha along with nitric oxide. Additionally, SecA2 reduces gamma interferon-induced MHC II levels, which could impact antigen presentation to CD4+ T cells.

Source: microbiolspec April 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TBTB2-0013-2016
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