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EcoSal Plus

Domain 4:

Synthesis and Processing of Macromolecules

Type V Secretion in Gram-Negative Bacteria

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.
  • Author: Harris D. Bernstein1
  • Editors: Maria Sandkvist2, Eric Cascales3, Peter J. Christie4
    Affiliations: 1: Genetics and Biochemistry Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892; 2: Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan; 3: CNRS Aix-Marseille Université, Mediterranean Institute of Microbiology, Marseille, France; 4: Department of Microbiology and Molecular Genetics, McGovern Medical School, Houston, Texas
  • Received 27 August 2018 Accepted 05 December 2018 Published 06 March 2019
  • Address correspondence to Harris D. Bernstein, [email protected]
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  • Abstract:

    Type V, or “autotransporter,” secretion is a term used to refer to several simple protein export pathways that are found in a wide range of Gram-negative bacteria. Autotransporters are generally single polypeptides that consist of an extracellular (“passenger”) domain and a β barrel domain that anchors the protein to the outer membrane (OM). Although it was originally proposed that the passenger domain is secreted through a channel formed solely by the covalently linked β barrel domain, experiments performed primarily on the type Va, or “classical,” autotransporter pathway have challenged this hypothesis. Several lines of evidence strongly suggest that both the secretion of the passenger domain and the membrane integration of the β barrel domain are catalyzed by the arrel ssembly achinery (Bam) complex, a conserved hetero-oligomer that plays an essential role in the assembly of most integral OM proteins. The secretion reaction appears to be driven at least in part by the folding of the passenger domain in the extracellular space. Although many aspects of autotransporter biogenesis remain to be elucidated, it will be especially interesting to determine whether the different classes of proteins that fall under the type V rubric—most of which have not been examined in detail—are assembled by the same basic mechanism as classical autotransporters.

  • Citation: Bernstein H. 2019. Type V Secretion in Gram-Negative Bacteria, EcoSal Plus 2019; doi:10.1128/ecosalplus.ESP-0031-2018

Article Version

This article is an updated version of the following content:


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Type V, or “autotransporter,” secretion is a term used to refer to several simple protein export pathways that are found in a wide range of Gram-negative bacteria. Autotransporters are generally single polypeptides that consist of an extracellular (“passenger”) domain and a β barrel domain that anchors the protein to the outer membrane (OM). Although it was originally proposed that the passenger domain is secreted through a channel formed solely by the covalently linked β barrel domain, experiments performed primarily on the type Va, or “classical,” autotransporter pathway have challenged this hypothesis. Several lines of evidence strongly suggest that both the secretion of the passenger domain and the membrane integration of the β barrel domain are catalyzed by the arrel ssembly achinery (Bam) complex, a conserved hetero-oligomer that plays an essential role in the assembly of most integral OM proteins. The secretion reaction appears to be driven at least in part by the folding of the passenger domain in the extracellular space. Although many aspects of autotransporter biogenesis remain to be elucidated, it will be especially interesting to determine whether the different classes of proteins that fall under the type V rubric—most of which have not been examined in detail—are assembled by the same basic mechanism as classical autotransporters.

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Image of Figure 1
Figure 1

Proteins in type V (and type V-like) secretion pathways consist of a 12-stranded (red), 16-stranded (green), or predicted 8-stranded (pink) β barrel domain and an extracellular (“passenger”) domain that typically folds into a β-helical (blue), mixed coiled-coil/β roll/β prism (purple) or globular (brown) structure. The 16-stranded β barrel domains are members of the Omp85 superfamily and contain periplasmic POTRA domains. In most cases the β barrel and passenger domains are covalently linked, but in the type Vb pathway the β barrel domain and the extracellular component (“exoprotein”) are separate polypeptides. In the type Vc pathway both domains are formed through the assembly of three identical subunits. The passenger domain is located at the N terminus of the protein in the type Va, Vb, Vc, and Vd pathways, but it is found at the C terminus in the type Ve pathway. In the type V-like pathway the extracellular domain is located in a loop that connects the first two β strands of the β barrel domain. Crystal structures of representative polypeptides from each pathway are shown. α-helical segments are colored red and β strands are colored yellow. The structures include the pertactin (Prn) passenger domain ( 4 ) (PDB code 1DAB), a fragment of the HMW1 exoprotein ( 98 ) (PDB code 2ODL), a fragment of the EibD passenger domain ( 24 ) (PDB code 2XQH), the phospholipase D (PlpD) passenger domain ( 34 ) (PDB code 5FYA), the invasin (Inv) passenger domain ( 28 ) (1CWV), the SabA extracellular domain ( 36 ) (PDB code 4O5J), and the NalP, FhaC, Hia, and intimin (Int) β barrel domains (PDB codes 1UYO, 4QKY, 2GR7, and 4E1S) ( 10 , 18 , 29 , 99 ). The helix inside the FhaC β barrel was generated from a neighboring asymmetric unit in the crystal lattice. No structures of β barrel domains of type Vd or type V-like proteins have been reported. Modified from ( 100 ), with permission.

Citation: Bernstein H. 2019. Type V Secretion in Gram-Negative Bacteria, EcoSal Plus 2019; doi:10.1128/ecosalplus.ESP-0031-2018
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Image of Figure 2
Figure 2

Available evidence suggests that the β barrel domain (red) begins to fold in the periplasm (step I) and incorporates the C terminus of the passenger domain (blue) in a hairpin conformation. At this stage the β barrel domain interacts with the molecular chaperone Skp. The partially folded β barrel domain is then targeted to the OM, where it binds to BamA, BamB, and BamD in a stereospecific fashion (step II). The surface exposure of the passenger domain and the initiation of translocation require an additional assembly step in which the β barrel domain moves into the membrane (step III). Both autotransporter and BamA β barrels are in an open conformation at this stage. Translocation involves the progressive movement of passenger domain segments from the chaperone SurA to the POTRA domains of BamA to the transport channel and is driven at least in part by vectorial folding (step IV). Following the completion of translocation the hairpin is resolved (step V), and an unusual lipid-facing basic or large polar residue found in at least a subset of autotransporters facilitates the completion of β barrel domain assembly (step VI). The β barrel domain is then released from the Bam complex, and, in some cases, the two domains are separated by an intrabarrel cleavage or an extrabarrel cleavage mediated by a -acting protease (step VII). In the Bam complex contains five subunits, but BamC and BamE have been omitted for clarity. Modified from ( 57 , 100 ), with permission.

Citation: Bernstein H. 2019. Type V Secretion in Gram-Negative Bacteria, EcoSal Plus 2019; doi:10.1128/ecosalplus.ESP-0031-2018
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