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Type V Secretion Systems in Bacteria

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  • Authors: Enguo Fan1, Nandini Chauhan2, D. B. R. K. Gupta Udatha3, Jack C. Leo4, Dirk Linke5
  • Editor: Indira T. Kudva6
    Affiliations: 1: Institute of Biochemistry and Molecular Biology, University of Freiburg, Freiburg D-79104, Germany; 2: Department of Biosciences, University of Oslo, Blindern, 0316 Oslo, Norway; 3: Department of Biosciences, University of Oslo, Blindern, 0316 Oslo, Norway; 4: Department of Biosciences, University of Oslo, Blindern, 0316 Oslo, Norway; 5: Department of Biosciences, University of Oslo, Blindern, 0316 Oslo, Norway; 6: National Animal Disease Center, Agricultural Research Service, U.S. Department of Agriculture, Ames, IA
  • Source: microbiolspec February 2016 vol. 4 no. 1 doi:10.1128/microbiolspec.VMBF-0009-2015
  • Received 27 February 2015 Accepted 29 April 2015 Published 19 February 2016
  • Dirk Linke, [email protected]
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  • Abstract:

    Type V secretion denotes a variety of secretion systems that cross the outer membrane in Gram-negative bacteria but that depend on the Sec machinery for transport through the inner membrane. They are possibly the simplest bacterial secretion systems, because they consist only of a single polypeptide chain (or two chains in the case of two-partner secretion). Their seemingly autonomous transport through the outer membrane has led to the term “autotransporters” for various subclasses of type V secretion. In this chapter, we review the structure and function of these transporters and review recent findings on additional factors involved in the secretion process, which have put the term “autotransporter” to debate.

  • Citation: Fan E, Chauhan N, Udatha D, Leo J, Linke D. 2016. Type V Secretion Systems in Bacteria. Microbiol Spectrum 4(1):VMBF-0009-2015. doi:10.1128/microbiolspec.VMBF-0009-2015.


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Type V secretion denotes a variety of secretion systems that cross the outer membrane in Gram-negative bacteria but that depend on the Sec machinery for transport through the inner membrane. They are possibly the simplest bacterial secretion systems, because they consist only of a single polypeptide chain (or two chains in the case of two-partner secretion). Their seemingly autonomous transport through the outer membrane has led to the term “autotransporters” for various subclasses of type V secretion. In this chapter, we review the structure and function of these transporters and review recent findings on additional factors involved in the secretion process, which have put the term “autotransporter” to debate.

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Schematic domain organization among the five subcategories of known type V bacterial autotransporter proteins. The overall organization is labeled according to four major and common features ( 175 ): signal sequence, passenger, linker, and β-barrel. Note that similar features are based only on functional considerations in this context; they are not necessarily homologous. An example is the linker depicted for TpsA proteins here, which is the TPS domain that targets TpsA proteins for secretion by its TpsB partner. For a detailed discussion of the various linker regions and their function(s) see reference 175 . The figure also shows the major families of the functional domains in the type Va autotransporter sequences of bacterial species that were defined through hidden Markov model–based phylogenetic analysis of 1,210 bacterial genomes ( 19 ).

Source: microbiolspec February 2016 vol. 4 no. 1 doi:10.1128/microbiolspec.VMBF-0009-2015
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Experimental structures of passenger domains from type V secretion systems. Examples from type Va (classical autotransporters), type Vb (TpsA proteins), type Vc (trimeric autotransporter adhesins), and type Ve (inverse autotransporters) are included. Structures are shown in cartoon representation. β-solenoid structures are orange, with extrahelical domains and elements in yellow. β-prism domains are purple and coiled coils are red; connector elements are cyan. For type Vc proteins, each chain is colored with a slightly different hue. Chloride ions within coiled-coil stalks are represented by green spheres. Immunoglobulin-like domains are green, and C-type lectin-like domains blue. The structures representing type Va passengers are the pertactin passenger domain (PDB ID: 1DAB), the Hbp passenger (1WXR), and a fragment of the antigen 43 passenger (4KH3). TpsA proteins are represented by the FHA and HMW1 Tps domains (1RWR and 2ODL, respectively). Trimeric autotransporter adhesin passenger domains are represented by large fragments from EibD (2XQH) and SadA (2YO1), the Trp ring and GIN domains of the BadA head (3DX9), the head domains of YadA (1P9H), UspA1 (3NTN) and NadA (4CJD), and the region of the YadA stalk transitioning from right-handed (at the top) to left-handed (at the bottom) supercoiling. Fragments from the FdeC (4E9L) and invasin (1CWV) passenger domains represent type Ve passengers. The structures are oriented so that the portion of passenger domains distal to the outer membrane is pointing toward the top of the page. Note that for types Va, Vb, and Vc, the distal end is the N-terminus, whereas for type Ve passengers the C-terminus is distal.

Source: microbiolspec February 2016 vol. 4 no. 1 doi:10.1128/microbiolspec.VMBF-0009-2015
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Full-length structures of type V–secreted proteins. The only experimental structure of a complete autotransporter is that of EstA (PDB ID: 3KVN). Efforts using experimental structures of fragments, homology, and modeling have generated models for full-length fibers of TpsA proteins (exemplified here as the FHA model with a total length of ∼46 nm [ 117 ]) and trimeric autotransporter adhesins, exemplified by the long SadA fiber (total length ∼108 nm) ( 16 ), and the much shorter YadA fiber (∼35 nm) ( 61 ). In addition, the structure of FhaC (2QDZ) is shown. The structures of the different type V subclasses are to approximate scale, and in addition, the EstA structure is shown in close-up. β-barrel domains are blue, linkers are yellow, the lipase domain of EstA is pink, β-solenoids are orange, extrahelical extensions are yellow, connector elements are cyan, coiled coils are red, and periplasmic domains are green. The approximate span of the outer membrane is shown as a gray bar.

Source: microbiolspec February 2016 vol. 4 no. 1 doi:10.1128/microbiolspec.VMBF-0009-2015
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Experimental structures of translocation units of type V secretion systems. Examples from type Va (classical autotransporters), type Vb (TpsB proteins), type Vc (trimeric autotransporter adhesins), and type Ve (inverse autotransporters) are included. Structures are shown in cartoon representation. β-barrel domains are blue, linker regions or intrabarrel α-helices are yellow, significant extracellular loops are brown, periplasmically located domains and extensions are green, coiled-coil stalks are red, and connector elements are cyan. For type Vc proteins, each chain is colored with a slightly different hue. All proteins are oriented such that the extracellular face of the β-barrel is pointing toward the top of the page, and the approximate positioning of the outer membrane is shown in gray. Note that for type Va and type Vc translocation domains, the N-termini of the proteins are extracellular, whereas for types Vb and Ve, the N-termini are periplasmic. Type Va translocation domains are represented by structures from NalP (PDB ID: 1UYN), EspP (2QOM), and AIDA-I (4MEE). TpsB proteins are represented by FhaC (2QDZ), with two POTRA domains. Type Vc translocation domains are exemplified by the YadA (2LME) and Hia (3EMO) structures. The intimin translocation domain (4E1S) and LysM (2MPW, with additional α-helix highlighted) represent type Ve translocation and periplasmic domains. β-barrel proteins involved in the biogenesis of type V–secreted proteins, BamA and TamA. The structures of TamA (4C00) and BamA (4C4V) from are also shown, with the unstable β-strand 16 highlighted (the coloring otherwise corresponds to panel . TamA has three N-terminal periplasmic POTRA domains. The BamA has five POTRA domains; one is part of the β-barrel structure and the other four have been crystallized separately (2QDF). The approximate span of the outer membrane is shown as a gray bar.

Source: microbiolspec February 2016 vol. 4 no. 1 doi:10.1128/microbiolspec.VMBF-0009-2015
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Overview of the liposome-based system for type Va and Vb analysis. The test substrates are prepared as urea-denatured, purified proteins or by using spheroplasts. Translocation may need additional factors added to the proteoliposome mix, such as chaperone(s) for urea-denatured substrates. The success of the translocation is then monitored either by protease accessibility assays or by checking heat-modifiability (a unique feature of bacterial β-barrels).

Source: microbiolspec February 2016 vol. 4 no. 1 doi:10.1128/microbiolspec.VMBF-0009-2015
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Models of outer membrane insertion and passenger secretion in type Va autotransporters. Models of membrane insertion. Membrane insertion of autotransporters (and other outer membrane β-barrel proteins) depends on BamA (depicted in light gray). The autotransporter itself is shown in dark gray. Currently, three models are envisaged to explain membrane insertion and initiation of autotransport. In model 1, BamA catalyzes the insertion of the β-barrel domain of the autotransporter, after which hairpin formation and passenger domain secretion proceed autonomously. In model 2, membrane insertion and hairpin formation happen concomitantly. A third model (model 3) has been proposed, where a semifolded “protobarrel” already containing the hairpin is formed in the periplasm. This is then inserted into the outer membrane by BamA. All three models lead to the autotransporter β-barrel being folded and inserted into the outer membrane and passenger secretion proceeding via a hairpin from the C- to the N-terminus (model 4). Note that BamA may also be involved in passenger secretion (see panel . Small black arrows depict the direction of secretion; large light arrows depict the flow of events. The N-terminus of the autotransporter is denoted by an N for clarity. Models of passenger secretion. Two models exist where passenger secretion is autonomous, i.e., genuine autotransport (models 1 and 2). In the threading model (model 1), the passenger is secreted through the pore of the autotransporter β-barrel (in dark gray) N-terminus first. The hairpin model (model 2) is preferred over this because it is more in line with current biochemical evidence (see text); here, the C-terminus of the passenger domain (the linker region) forms a hairpin within the pore of the autotransporter β-barrel. Secretion then proceeds C to N. In the third model of passenger secretion, a secondary protein (BamA or TamA, in light gray) assists in passenger secretion, possibly by forming a hybrid barrel with the autotransporter as depicted here. Small gray arrows depict the direction of secretion; the N-terminus of the autotransporter is denoted by an N for clarity.

Source: microbiolspec February 2016 vol. 4 no. 1 doi:10.1128/microbiolspec.VMBF-0009-2015
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