Deciphering the Xcp Pseudomonas aeruginosa Type II Secretion Machinery through Multiple Interactions with Substrates

Douzi, Badreddine; Ball, Geneviève; Cambillau, Christian; Tegoni, Mariella; Voulhoux, Romé

doi:10.1074/jbc.m111.294843

Cited by 88 publications

(126 citation statements)

References 31 publications

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“…Here it is suggested that the exotoxin sitting on the grown pseudopilus induces conformational changes in the secretin, which results in the opening of the periplasmic gate and the final release of the toxin (37,57). If a pseudopilus triggers opening of the Thermus PilQ complex, thereby enabling DNA uptake, a direct interaction of the pseudopilus structures and the PilQ complex is a prerequisite.…”

Section: Journal Of Biological Chemistrymentioning

confidence: 99%

Unusual N-terminal ααβαββα Fold of PilQ from Thermus thermophilus Mediates Ring Formation and Is Essential for Piliation

Burkhardt

Vonck

Langer

et al. 2012

Journal of Biological Chemistry

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Background:Secretins are key components of complex DNA and protein transport machineries. Results: An unusual secretin ␣␣␤␣␤␤␣ fold was identified as a ring-building motif essential for piliation but not for transformation. Conclusion: Type IV pilus structures are not essential for transformation in T. thermophilus. Significance: This is the first report of a ring-building domain of a unique secretin complex in T. thermophilus.

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Section: Journal Of Biological Chemistrymentioning

confidence: 99%

Unusual N-terminal ααβαββα Fold of PilQ from Thermus thermophilus Mediates Ring Formation and Is Essential for Piliation

Burkhardt

Vonck

Langer

et al. 2012

Journal of Biological Chemistry

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“…7). This result was perhaps not surprising given the numerous studies that have demonstrated several different points of interaction between GspC and GspD (45)(46)(47)(48); as a result, coexpression of ExeC with ExeD would more closely resemble a wild-type situation than expression of ExeD alone. The necessity for additional, highly conserved assembly factors, such as the Bam complex, has not been determined in A. hydrophila, although Bam-independent assembly of the T2SS secretin has been shown for other bacteria (49,50).…”

Section: Discussionmentioning

confidence: 81%

Alterations in Peptidoglycan Cross-Linking Suppress the Secretin Assembly Defect Caused by Mutation of GspA in the Type II Secretion System

et al. 2017

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In Gram-negative bacteria, the peptidoglycan (PG) cell wall is a significant structural barrier for outer membrane protein assembly. In Aeromonas hydrophila, outer membrane multimerization of the type II secretion system (T2SS) secretin ExeD requires the function of the inner membrane assembly factor complex ExeAB. The putative mechanism of the complex involves the reorganization of PG and localization of ExeD, whereby ExeA functions by interacting with PG to form a site for secretin assembly and ExeB forms an interaction with ExeD. This mechanism led us to hypothesize that increasing the pore size of PG would circumvent the requirement for ExeA in the assembly of the ExeD secretin. Growth of A. hydrophila in 270 mM Gly reduced PG cross-links by approximately 30% and led to the suppression of secretin assembly defects in exeA strains and in those expressing ExeA mutants by enabling localization of the secretin in the outer membrane. We also established a heterologous ExeD assembly system in Escherichia coli and showed that ExeAB and ExeC are the only A. hydrophila proteins required for the assembly of the ExeD secretin in E. coli and that ExeAB-independent assembly of ExeD can occur upon overexpression of the D,D-carboxypeptidase PBP 5. These results support an assembly model in which, upon binding to PG, ExeA induces multimerization and pore formation in the sacculus, which enables ExeD monomers to interact with ExeB and assemble into a secretin that both is inserted in the outer membrane and crosses the PG layer to interact with the inner membrane platform of the T2SS. IMPORTANCEThe PG layer imposes a strict structural impediment for the assembly of macromolecular structures that span the cell envelope and serve as virulence factors in Gram-negative species. This work revealed that by decreasing PG crosslinking by growth in Gly, the absolute requirement for the PG-binding activity of ExeA in the assembly of the ExeD secretin was alleviated in A. hydrophila. In a heterologous assembly model in E. coli, expression of the carboxypeptidase PBP 5 could relieve the requirement for ExeAB in the assembly of the ExeD secretin. These results provide some mechanistic details of the ExeAB assembly complex function, in which the PG-binding and oligomerization functions of ExeAB are used to create a pore in the PG that is required for secretin assembly.KEYWORDS type II secretion system, peptidoglycan, secretin assembly T he secretion of protein toxins and enzymes via the type II secretion system (T2SS) is an important virulence mechanism as well as a major route of scavenging enzyme secretion and surface protein assembly for many Gram-negative bacteria (1-4). The T2SS is a large complex composed of 12 to 15 highly conserved proteins designated

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“…In this case, the exoprotein could adopt a secretion-competent conformation prior to secretion and another conformation once released in the extracellular medium [138]. This sequence of events is probably not the case with P. aeruginosa and V. cholerae T2SSs for which interactions found between substrates and secreton components were detected using purified secreted proteins [41,61,70]. Obviously the question of specific substrate recognition is far from being resolved.…”

Section: Substrate Recognition and Transport By The T2ss Machinementioning

confidence: 99%

“…However, the replacement of the intermediary domain between TM and HR called TM/HR (figure 4) leads to secretion defect, suggesting that this domain plays an essential role in specificity and potentially in substrate recognition. Recently, a set of in vitro experiments has revealed direct interactions between purified XcpP C and two substrates of the Xcp T2SS, the elastase (LasB) and the lipase (LipA) [70]. Importantly, no interaction was detected using the substrate of the second P. aeruginosa T2SS (Hxc), i.e.…”

Section: The Outer Membrane Secretinmentioning

confidence: 99%

On the path to uncover the bacterial type II secretion system

Douzi

Filloux

Voulhoux

2012

Phil. Trans. R. Soc. B

Self Cite

103

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Gram-negative bacteria have evolved several secretory pathways to release enzymes or toxins into the surrounding environment or into the target cells. The type II secretion system (T2SS) is conserved in Gram-negative bacteria and involves a set of 12 to 16 different proteins. Components of the T2SS are located in both the inner and outer membranes where they assemble into a supramolecular complex spanning the bacterial envelope, also called the secreton. The T2SS substrates transiently go through the periplasm before they are translocated across the outer membrane and exposed to the extracellular milieu. The T2SS is unique in its ability to promote secretion of large and sometimes multimeric proteins that are folded in the periplasm. The present review describes recently identified protein–protein interactions together with structural and functional advances in the field that have contributed to improve our understanding on how the type II secretion apparatus assembles and on the role played by individual proteins of this highly sophisticated system.

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Deciphering the Xcp Pseudomonas aeruginosa Type II Secretion Machinery through Multiple Interactions with Substrates

Cited by 88 publications

References 31 publications

Unusual N-terminal ααβαββα Fold of PilQ from Thermus thermophilus Mediates Ring Formation and Is Essential for Piliation

Unusual N-terminal ααβαββα Fold of PilQ from Thermus thermophilus Mediates Ring Formation and Is Essential for Piliation

Alterations in Peptidoglycan Cross-Linking Suppress the Secretin Assembly Defect Caused by Mutation of GspA in the Type II Secretion System

On the path to uncover the bacterial type II secretion system

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