scholarly journals Structure of the mycobacterial ESX-5 Type VII Secretion System hexameric pore complex

2020 ◽  
Author(s):  
Kathrine S. H. Beckham ◽  
Christina Ritter ◽  
Grzegorz Chojnowski ◽  
Edukondalu Mullapudi ◽  
Mandy Rettel ◽  
...  
Keyword(s):  
Cell Envelope ◽  
Secretion System ◽  
Transmembrane Helices ◽  
Membrane Protein Complex ◽  
Virulence Proteins ◽  
The Core ◽  
Type Vii Secretion ◽  
Cryo Electron Microscopy ◽  
Core Components ◽  
Type Vii Secretion System

AbstractTo establish an infection, pathogenic mycobacteria use the Type VII secretion or ESX system to secrete virulence proteins across their cell envelope. The five ESX systems (ESX-1 to ESX-5) have evolved diverse functions in the cell, with the ESX-5 found almost exclusively in pathogens. Here we present a high-resolution cryo-electron microscopy structure of the hexameric ESX-5 Type VII secretion system. This 2.1 MDa membrane protein complex is built by a total of 30 subunits from six protomeric units, which are composed of the core components EccB5, EccC5, two copies of EccD5, and EccE5. The hexameric assembly of the overall ESX-5 complex is defined by specific inter-protomer interactions mediated by EccB5 and EccC5. The central transmembrane pore is formed by six pairs of EccC5 transmembrane helices that adopt a closed conformation in the absence of substrate in our structure. On the periplasmic face of the ESX-5 complex, we observe an extended arrangement of the six EccB5 subunits around a central cleft. Our structural findings provide molecular details of ESX-5 assembly and observations of the central secretion pore, which reveal insights into possible gating mechanisms used to regulate the transport of substrates.

scholarly journals Structures of EccB1 and EccD1 from the core complex of the mycobacterial ESX-1 type VII secretion system

2016 ◽  
Vol 16 (1) ◽  
Author(s):  
Jonathan M. Wagner ◽  
Sum Chan ◽  
Timothy J. Evans ◽  
Sara Kahng ◽  
Jennifer Kim ◽  
...  
Keyword(s):  
Secretion System ◽  
Core Complex ◽  
The Core ◽  
Type Vii Secretion ◽  
Type Vii Secretion System

scholarly journals Structure and dynamics of a mycobacterial type VII secretion system

Nature ◽  
2021 ◽  
Author(s):  
Catalin M. Bunduc ◽  
Dirk Fahrenkamp ◽  
Jiri Wald ◽  
Roy Ummels ◽  
Wilbert Bitter ◽  
...  
Keyword(s):  
Protein Transport ◽  
Cell Envelope ◽  
Transport Systems ◽  
Transmembrane Helices ◽  
Secretion Systems ◽  
Type Vii Secretion ◽  
Membrane Complex ◽  
Three Bundles ◽  
Type Vii Secretion System ◽  
Inner Membrane Complex

AbstractMycobacterium tuberculosis is the cause of one of the most important infectious diseases in humans, which leads to 1.4 million deaths every year1. Specialized protein transport systems—known as type VII secretion systems (T7SSs)—are central to the virulence of this pathogen, and are also crucial for nutrient and metabolite transport across the mycobacterial cell envelope2,3. Here we present the structure of an intact T7SS inner-membrane complex of M. tuberculosis. We show how the 2.32-MDa ESX-5 assembly, which contains 165 transmembrane helices, is restructured and stabilized as a trimer of dimers by the MycP5 protease. A trimer of MycP5 caps a central periplasmic dome-like chamber that is formed by three EccB5 dimers, with the proteolytic sites of MycP5 facing towards the cavity. This chamber suggests a central secretion and processing conduit. Complexes without MycP5 show disruption of the EccB5 periplasmic assembly and increased flexibility, which highlights the importance of MycP5 for complex integrity. Beneath the EccB5–MycP5 chamber, dimers of the EccC5 ATPase assemble into three bundles of four transmembrane helices each, which together seal the potential central secretion channel. Individual cytoplasmic EccC5 domains adopt two distinctive conformations that probably reflect different secretion states. Our work suggests a previously undescribed mechanism of protein transport and provides a structural scaffold to aid in the development of drugs against this major human pathogen.

scholarly journals Assisted assembly of bacteriophage T7 core components for genome translocation across the bacterial envelope

2021 ◽  
Vol 118 (34) ◽  
pp. e2026719118
Author(s):  
Mar Pérez-Ruiz ◽  
Mar Pulido-Cid ◽  
Juan Román Luque-Ortega ◽  
José María Valpuesta ◽  
Ana Cuervo ◽  
...  
Keyword(s):  
Bacteriophage T7 ◽  
Dna Translocation ◽  
Oligomeric State ◽  
Viral Dna ◽  
The Core ◽  
Cryo Electron Microscopy ◽  
Core Proteins ◽  
Core Components ◽  
Bacterial Cytoplasm ◽  
Bacterial Peptidoglycan

In most bacteriophages, genome transport across bacterial envelopes is carried out by the tail machinery. In viruses of the Podoviridae family, in which the tail is not long enough to traverse the bacterial wall, it has been postulated that viral core proteins assembled inside the viral head are translocated and reassembled into a tube within the periplasm that extends the tail channel. Bacteriophage T7 infects Escherichia coli, and despite extensive studies, the precise mechanism by which its genome is translocated remains unknown. Using cryo-electron microscopy, we have resolved the structure of two different assemblies of the T7 DNA translocation complex composed of the core proteins gp15 and gp16. Gp15 alone forms a partially folded hexamer, which is further assembled upon interaction with gp16 into a tubular structure, forming a channel that could allow DNA passage. The structure of the gp15–gp16 complex also shows the location within gp16 of a canonical transglycosylase motif involved in the degradation of the bacterial peptidoglycan layer. This complex docks well in the tail extension structure found in the periplasm of T7-infected bacteria and matches the sixfold symmetry of the phage tail. In such cases, gp15 and gp16 that are initially present in the T7 capsid eightfold-symmetric core would change their oligomeric state upon reassembly in the periplasm. Altogether, these results allow us to propose a model for the assembly of the core translocation complex in the periplasm, which furthers understanding of the molecular mechanism involved in the release of T7 viral DNA into the bacterial cytoplasm.

scholarly journals Structure of EspB from the ESX-1 Type VII Secretion System and Insights into its Export Mechanism

Structure ◽  
2015 ◽  
Vol 23 (3) ◽  
pp. 571-583 ◽  
Author(s):  
Matthew Solomonson ◽  
Dheva Setiaputra ◽  
Karl A.T. Makepeace ◽  
Emilie Lameignere ◽  
Evgeniy V. Petrotchenko ◽  
...  
Keyword(s):  
Secretion System ◽  
Type Vii Secretion ◽  
Type Vii Secretion System

A Chimeric EccB-MycP Fusion Protein is Functional and a Stable Component of the ESX-5 Type VII Secretion System Membrane Complex

2020 ◽  
Vol 432 (4) ◽  
pp. 1265-1278 ◽  
Author(s):  
Vincent J.C. van Winden ◽  
Catalin M. Bunduc ◽  
Roy Ummels ◽  
Wilbert Bitter ◽  
Edith N.G. Houben
Keyword(s):  
Fusion Protein ◽  
Secretion System ◽  
Stable Component ◽  
Type Vii Secretion ◽  
Membrane Complex ◽  
Type Vii Secretion System

scholarly journals The Ess/Type VII secretion system of Staphylococcus aureus shows unexpected genetic diversity

BMC Genomics ◽  
2016 ◽  
Vol 17 (1) ◽  
Author(s):  
Ben Warne ◽  
Catriona P. Harkins ◽  
Simon R. Harris ◽  
Alexandra Vatsiou ◽  
Nicola Stanley-Wall ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Staphylococcus Aureus ◽  
Secretion System ◽  
Type Vii Secretion ◽  
Type Vii Secretion System

scholarly journals A Duplicated ESAT-6 Region of ESX-5 Is Involved in Protein Export and Virulence of Mycobacteria

2015 ◽  
Vol 83 (11) ◽  
pp. 4349-4361 ◽  
Author(s):  
Swati Shah ◽  
Joe R. Cannon ◽  
Catherine Fenselau ◽  
Volker Briken
Keyword(s):  
Secretion System ◽  
Bacterial Virulence ◽  
Inflammasome Activation ◽  
Zebrafish Model ◽  
Content Type ◽  
Type Vii Secretion ◽  
Specific Subset ◽  
Host Cell Death ◽  
Type Vii Secretion System

ABSTRACTThe ESX-5 secretion system ofMycobacterium tuberculosisis important for bacterial virulence and for the secretion of the large PE/PPE protein family, whose genes constitute 10% of theM. tuberculosisgenome. A four-gene region of the ESX-5 system is duplicated three times in theM. tuberculosisgenome, but the functions of these duplicates are unknown. Here we investigated one of these duplicates: the region carrying theesxI,esxJ,ppe15, andpe8genes (ESX-5a). An ESX-5a deletion mutant in the model systemM. marinumbackground was deficient in the secretion of some members of the PE/PPE family of proteins. Surprisingly, we also identified other proteins that are not members of this family, thus expanding the range of ESX-5 secretion substrates. In addition, we demonstrated that ESX-5a is important for the virulence ofM. marinumin the zebrafish model. Furthermore, we showed the role of theM. tuberculosisESX-5a region in inflammasome activation but not host cell death induction, which is different from the case for theM. tuberculosisESX-5 system. In conclusion, the ESX-5a region is nonredundant with its ESX-5 paralog and is necessary for secretion of a specific subset of proteins inM. tuberculosisandM. marinumthat are important for bacterial virulence ofM. marinum. Our findings point to a role for the three ESX-5 duplicate regions in the selection of substrates for secretion via ESX-5, and hence, they provide the basis for a refined model of the molecular mechanism of this type VII secretion system.

scholarly journals Crosstalk between the ancestral type VII secretion system ESX-4 and other T7SS in Mycobacterium marinum

iScience ◽  
2021 ◽  
pp. 103585
Author(s):  
Yuchen Wang ◽  
Yuting Tang ◽  
Chen Lin ◽  
Junli Zhang ◽  
Juntao Mai ◽  
...  
Keyword(s):  
Secretion System ◽  
Mycobacterium Marinum ◽  
Type Vii Secretion ◽  
Type Vii Secretion System ◽  
Ancestral Type
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