Substrate-Activated Conformational Switch on Chaperones Encodes a Targeting Signal in Type III Secretion

Chen, Li; Ai, Xuan; Portaliou, Athina G; Minetti, Conceição A.S.A.; Remeta, David P.; Economou, Anastassios; Kalodimos, Charalampos G.

doi:10.1016/j.celrep.2013.02.025

Cited by 39 publications

(54 citation statements)

References 48 publications

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“…Indeed, InvE, a Salmonella homolog of SepL and YopN, does not interact with either the translocators or their chaperone individually but can form a complex when all these proteins are present (53). It has recently been shown by using nuclear magnetic resonance (NMR) spectroscopy that the interaction between EscN and CesAB occurs only after binding of CesAB to EspA, which results in conformational changes in CesAB exposing a targeting signal to EscN (54). Concluding remarks.…”

Section: Wclmentioning

confidence: 99%

SepD/SepL-Dependent Secretion Signals of the Type III Secretion System Translocator Proteins in Enteropathogenic Escherichia coli

Deng

2015

J. Bacteriol.

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The type III protein secretion system (T3SS) encoded by the locus of enterocyte effacement (LEE) is essential for the pathogenesis of attaching/effacing bacterial pathogens, including enteropathogenic Escherichia coli (EPEC), enterohemorrhagic E. coli (EHEC), and Citrobacter rodentium. These pathogens use the T3SS to sequentially secrete three categories of proteins: the T3SS needle and inner rod protein components; the EspA, EspB, and EspD translocators; and many LEE-and non-LEE-encoded effectors. SepD and SepL are essential for translocator secretion, and mutations in either lead to hypersecretion of effectors. However, how SepD and SepL control translocator secretion and secretion hierarchy between translocators and effectors is poorly understood. In this report, we show that the secreted T3SS components, the translocators, and both LEE-and non-LEE-encoded effectors all carry N-terminal type III secretion and translocation signals. These signals all behave like those of the effectors and are sufficient for mediating type III secretion and translocation by wild-type EPEC and hypersecretion by the sepD and sepL mutants. Our results extended previous observations and suggest that the secretion hierarchy of the different substrates is determined by a signal other than the N-terminal secretion signal. We identified a domain located immediately downstream of the N-terminal secretion signal in the translocator EspB that is required for SepD/SepL-dependent secretion. We further demonstrated that this EspB domain confers SepD/SepL-and CesAB-dependent secretion on the secretion signal of effector EspZ. Our results thus suggest that SepD and SepL control and regulate secretion hierarchy between translocators and effectors by recognizing translocator-specific export signals. IMPORTANCEMany bacterial pathogens use a syringe-like protein secretion apparatus, termed the type III protein secretion system (T3SS), to secrete and inject numerous proteins directly into the host cells to cause disease. The secreted proteins perform different functions at various stages during infection and are classified into three substrate categories (T3SS components, translocators, and effectors). They all contain secretion signals at their N termini, but how their secretion hierarchy is determined is poorly understood. Here, we show that the N-terminal secretion signals from different substrate categories all behave the same and do not confer substrate specificity. We further characterize the secretion signals of the translocators and identify a translocator-specific signal, demonstrating that substrate-specific secretion signals are required in regulating T3SS substrate hierarchy. T he type III secretion system (T3SS) is one of the best-studied bacterial protein secretion systems and plays a central role in the virulence and pathogenesis of a large number of medically and agriculturally important bacterial pathogens, including Yersinia, Salmonella, Pseudomonas, Shigella, and Escherichia spp. (1-3). The T3SS consists of a series of mu...

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Section: Wclmentioning

confidence: 99%

SepD/SepL-Dependent Secretion Signals of the Type III Secretion System Translocator Proteins in Enteropathogenic Escherichia coli

Deng

2015

J. Bacteriol.

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“…Recent structural data showed that some effector/chaperone complexes can form hexamers, which would fit the hexameric ATPase structure [217]. Interestingly, it was shown that targeting to the ATPase and secretion are largely independent events: while chaperone binding, rather than presence of the secretion signal, was required for association of a substrate with the ATPase, this was insufficient for secretion of the substrate [218].…”

Section: Type III Secretion Export Is a Multi-step Process With Many mentioning

confidence: 99%

Type III secretion systems: the bacterial flagellum and the injectisome

Diepold

Armitage

2015

Phil. Trans. R. Soc. B

183

175

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One contribution of 12 to a theme issue 'The bacterial cell envelope'. The flagellum and the injectisome are two of the most complex and fascinating bacterial nanomachines. At their core, they share a type III secretion system (T3SS), a transmembrane export complex that forms the extracellular appendages, the flagellar filament and the injectisome needle. Recent advances, combining structural biology, cryo-electron tomography, molecular genetics, in vivo imaging, bioinformatics and biophysics, have greatly increased our understanding of the T3SS, especially the structure of its transmembrane and cytosolic components, the transcriptional, post-transcriptional and functional regulation and the remarkable adaptivity of the system. This review aims to integrate these new findings into our current knowledge of the evolution, function, regulation and dynamics of the T3SS, and to highlight commonalities and differences between the two systems, as well as their potential applications.

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“…Because the internal diameter of the needle is on the order of 25 Å, it is believed that effectors must travel in a semi-unfolded state (2, 3) due to energy provided by an ATPase located at the base of the system (4 -6). Introduction of point mutations into key proteins of the T3SS have shown to be highly deleterious for the cytotoxicity potential of certain pathogens (7)(8)(9)(10)(11), and T3SS-deficient strains display attenuated infectivity in animal models (12)(13)(14), indicating that an understanding of T3SS formation and regulation mechanisms could lead to the development of strategies for infection control.…”

mentioning

confidence: 99%

Membrane and Chaperone Recognition by the Major Translocator Protein PopB of the Type III Secretion System of Pseudomonas aeruginosa

Discola

Förster

Boulay

et al. 2014

Journal of Biological Chemistry

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Background:The type III secretion system allows bacteria to inject effectors directly into the host cytoplasm through a translocation pore. Results: Translocator proteins were characterized in lipid-bound and chaperone-associated forms. Conclusion: Pseudomonas translocators use different regions to recognize their common chaperone and the eukaryotic membrane. Significance: Mapping of key regions in translocators provides a starting point for the potential development of novel antibacterials.

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Substrate-Activated Conformational Switch on Chaperones Encodes a Targeting Signal in Type III Secretion

Cited by 39 publications

References 48 publications

SepD/SepL-Dependent Secretion Signals of the Type III Secretion System Translocator Proteins in Enteropathogenic Escherichia coli

SepD/SepL-Dependent Secretion Signals of the Type III Secretion System Translocator Proteins in Enteropathogenic Escherichia coli

Type III secretion systems: the bacterial flagellum and the injectisome

Membrane and Chaperone Recognition by the Major Translocator Protein PopB of the Type III Secretion System of Pseudomonas aeruginosa

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