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EcoSal Plus

Domain 4:

Synthesis and Processing of Macromolecules

Architecture, Function, and Substrates of the Type II Secretion System

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.
  • Authors: Konstantin V. Korotkov1, and Maria Sandkvist2
  • Editors: Eric Cascales3, Peter J. Christie4
    Affiliations: 1: Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY 40506; 2: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109; 3: CNRS Aix-Marseille Université, Mediterranean Institute of Microbiology, Marseille, France; 4: Department of Microbiology and Molecular Genetics, McGovern Medical School, Houston, Texas
  • Received 24 October 2018 Accepted 21 December 2018 Published 15 February 2019
  • Address correspondence to Konstantin V. Korotkov, [email protected]; Maria Sandkvist, [email protected]
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  • Abstract:

    The type II secretion system (T2SS) delivers toxins and a range of hydrolytic enzymes, including proteases, lipases, and carbohydrate-active enzymes, to the cell surface or extracellular space of Gram-negative bacteria. Its contribution to survival of both extracellular and intracellular pathogens as well as environmental species of proteobacteria is evident. This dynamic, multicomponent machinery spans the entire cell envelope and consists of a cytoplasmic ATPase, several inner membrane proteins, a periplasmic pseudopilus, and a secretin pore embedded in the outer membrane. Despite the -envelope configuration of the T2S nanomachine, proteins to be secreted engage with the system first once they enter the periplasmic compartment via the Sec or TAT export system. Thus, the T2SS is specifically dedicated to their outer membrane translocation. The many sequence and structural similarities between the T2SS and type IV pili suggest a common origin and argue for a pilus-mediated mechanism of secretion. This minireview describes the structures, functions, and interactions of the individual T2SS components and the general architecture of the assembled T2SS machinery and briefly summarizes the transport and function of a growing list of T2SS exoproteins. Recent advances in cryo-electron microscopy, which have led to an increased understanding of the structure-function relationship of the secretin channel and the pseudopilus, are emphasized.

  • Citation: Korotkov K, Sandkvist M. 2019. Architecture, Function, and Substrates of the Type II Secretion System, EcoSal Plus 2019; doi:10.1128/ecosalplus.ESP-0034-2018

Article Version

This article is an updated version of the following content:


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The type II secretion system (T2SS) delivers toxins and a range of hydrolytic enzymes, including proteases, lipases, and carbohydrate-active enzymes, to the cell surface or extracellular space of Gram-negative bacteria. Its contribution to survival of both extracellular and intracellular pathogens as well as environmental species of proteobacteria is evident. This dynamic, multicomponent machinery spans the entire cell envelope and consists of a cytoplasmic ATPase, several inner membrane proteins, a periplasmic pseudopilus, and a secretin pore embedded in the outer membrane. Despite the -envelope configuration of the T2S nanomachine, proteins to be secreted engage with the system first once they enter the periplasmic compartment via the Sec or TAT export system. Thus, the T2SS is specifically dedicated to their outer membrane translocation. The many sequence and structural similarities between the T2SS and type IV pili suggest a common origin and argue for a pilus-mediated mechanism of secretion. This minireview describes the structures, functions, and interactions of the individual T2SS components and the general architecture of the assembled T2SS machinery and briefly summarizes the transport and function of a growing list of T2SS exoproteins. Recent advances in cryo-electron microscopy, which have led to an increased understanding of the structure-function relationship of the secretin channel and the pseudopilus, are emphasized.

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Image of Figure 1
Figure 1

A schematic diagram of topology and location of the conserved core components of the T2SS. The accessory components GspN, GspA, and GspB are not shown. A selection of the T2SS substrates of variable functions. Protein toxins include AB cholera toxin ( 139 ) and exotoxin A ( 140 ). Hydrolytic enzymes include VesB ( 68 ), lipase in complex with chaperone (shown in purple) ( 71 ), pullulanase ( 77 ), pectate lyase C ( 141 ), EHEC metalloprotease StcE ( 142 ), and aminopeptidase LapA ( 91 ). biofilm matrix protein RbmA is a scaffolding protein ( 143 , 144 ).

Citation: Korotkov K, Sandkvist M. 2019. Architecture, Function, and Substrates of the Type II Secretion System, EcoSal Plus 2019; doi:10.1128/ecosalplus.ESP-0034-2018
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Figure 2

The ATPase is hexameric GspE with C6 and C2 symmetries ( 20 ). A close-up view shows the Zn binding site, which is required for the function of GspE ( 14 , 145 ). Inner membrane components include the cytoplasmic domain of GspF ( 19 ), cytoplasmic domain of GspL in complex with N1 domain of GspE ( 16 ), periplasmic domain of GspL ( 26 ), periplasmic domain of GspM ( 25 ), the homology region (HR) domain of ETEC GspC ( 32 ), and the PDZ domain of GspC ( 29 ). The structure of periplasmic domain of GspL (XcpY) has been recently published ( 146 ). Regarding pseudopilus components, in the GspG pseudopilus model based on the cryo-EM reconstruction ( 50 ), a close-up view shows the Ca binding site of GspG, minor pseudopilin GspH ( 47 ), and the trimeric complex of ETEC GspK-GspI-GspJ ( 48 ), and a close-up view shows a double-Ca binding site of GspK. The structure of a homologous XcpX-XcpV-XcpW complex from has been recently reported ( 147 ).

Citation: Korotkov K, Sandkvist M. 2019. Architecture, Function, and Substrates of the Type II Secretion System, EcoSal Plus 2019; doi:10.1128/ecosalplus.ESP-0034-2018
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Figure 3

The side and top views of ETEC GspD-AspS complex ( 37 ), EPEC GspD ( 36 ), K-12 GspD ( 34 ), and GspD ( 35 ). A single secretin protomer is highlighted, with N1, N2, and N3 domains in shades of blue, the secretin domain in green, and the S domain in magenta. Several AspS protomers (brown) were omitted to clearly show the location of the S domain. The cap subdomain in the -type secretins is highlighted in orange. The N0 domains (purple) were not resolved in the available cryo-EM reconstructions due to flexibility. Instead, its approximate location is indicated ( 148 ). Note that the N1-N2 domains of EPEC GspD ( 36 ) and the N1 domain of GspD ( 35 ) have been placed as rigid fit models. Structures of pilotins in complex with the secretin S domains (magenta). Structures of -type ETEC AspS ( 37 ) and -type GspS ( 116 ) are shown.

Citation: Korotkov K, Sandkvist M. 2019. Architecture, Function, and Substrates of the Type II Secretion System, EcoSal Plus 2019; doi:10.1128/ecosalplus.ESP-0034-2018
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Examples of T2SS substrates

Citation: Korotkov K, Sandkvist M. 2019. Architecture, Function, and Substrates of the Type II Secretion System, EcoSal Plus 2019; doi:10.1128/ecosalplus.ESP-0034-2018

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