Tetratricopeptide repeats are essential for PcrH chaperone function in<i>Pseudomonas aeruginosa</i>type III secretion

Bröms, Jeanette E.; Edqvist, Petra J.; Försberg, Åke; Francis, Matthew S.

doi:10.1111/j.1574-6968.2005.00099.x

Cited by 36 publications

(45 citation statements)

References 42 publications

(81 reference statements)

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“…This was an unexpected result, in light of mutational analysis of PcrH, which predicted that the cleft of the chaperone would be involved in binding the major translocator (PopB), whereas the convex face contained the binding site for the minor translocator (PopD) (14). This potential discrepancy, however, can be explained by the structure of the PcrH-PopD complex presented here.…”

Section: Discussioncontrasting

confidence: 45%

“…This potential discrepancy, however, can be explained by the structure of the PcrH-PopD complex presented here. PcrH residues whose mutagenesis by Bröms et al (14) compromised expression and secretion of both PopB and PopD are shown in yellow in Fig. 5A; residues whose mutagenesis compromised expression and secretion uniquely of PopB are depicted in magenta.…”

Section: Discussionmentioning

confidence: 99%

“…This was an unexpected result, because mutagenesis experiments based on three-dimensional models of SycD and PcrH suggested that the concave cleft of the type II chaperones contains the binding site for the major, and not the minor, translocator protein (13,14). Thus, the structure of the PcrHPopD(47-56) complex presented here reveals that the concave region of the type II chaperone TPR fold can bind specific regions from both major and minor translocator proteins, which can presumably then wrap around the chaperone in distinct fashions.…”

Section: Binding Of the Popd Translocator To Pcrh Stabilizes Its Oligmentioning

confidence: 99%

“…The stoichiometry of the association between the hydrophobic translocator proteins and their cognate chaperone is still a matter of controversy. Although most hydrophobic translocators have been shown to be able to bind to their chaperones independently from one another, it is unclear if this occurs through the formation of distinct binary complexes (in which the chaperone binds each translocator individually) or if the same chaperone binds both translocators simultaneously by using distinct binding sites (13)(14)(15). Interestingly, the latter suggestion is related to the hypothesis that both translocator proteins may travel through the T3SS needle in complexed form (15).…”

mentioning

confidence: 95%

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Structural Basis of Chaperone Recognition of Type III Secretion System Minor Translocator Proteins

Job

Matteï

Lemaire

et al. 2010

Journal of Biological Chemistry

125

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The type III secretion system (T3SS) is a complex nanomachine employed by many Gram-negative pathogens, including the nosocomial agent Pseudomonas aeruginosa, to inject toxins directly into the cytoplasm of eukaryotic cells. A key component of all T3SS is the translocon, a proteinaceous channel that is inserted into the target membrane, which allows passage of toxins into target cells. In most bacterial species, two distinct membrane proteins (the "translocators") are involved in translocon formation, whereas in the bacterial cytoplasm, however, they remain associated to a common chaperone. To date, the strategy employed by a single chaperone to recognize two distinct translocators is unknown. Here, we report the crystal structure of a complex between the Pseudomonas translocator chaperone PcrH and a short region from the minor translocator PopD. PcrH displays a 7-helical tetratricopeptide repeat fold that harbors the PopD peptide within its concave region, originally believed to be involved in recognition of the major translocator, PopB. Point mutations introduced into the PcrH-interacting region of PopD impede translocator-chaperone recognition in vitro and lead to impairment of bacterial cytotoxicity toward macrophages in vivo. These results indicate that T3SS translocator chaperones form binary complexes with their partner molecules, and the stability of their interaction regions must be strictly maintained to guarantee bacterial infectivity. The PcrHPopD complex displays homologs among a number of pathogenic strains and could represent a novel, potential target for antibiotic development.

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Section: Discussioncontrasting

confidence: 45%

Section: Discussionmentioning

confidence: 99%

Section: Binding Of the Popd Translocator To Pcrh Stabilizes Its Oligmentioning

confidence: 99%

mentioning

confidence: 95%

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Structural Basis of Chaperone Recognition of Type III Secretion System Minor Translocator Proteins

Job

Matteï

Lemaire

et al. 2010

Journal of Biological Chemistry

125

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“…Class II chaperones interact with translocon proteins (589), whereas chaperones of flagellar T3S systems are referred to as class III chaperones (431). Chaperones of translocon proteins usually contain tandem tetratricopeptide repeats (TPRs), which are imperfect 34-amino-acid repeats that are also present in eukaryotic chaperones and are often involved in protein-protein interactions (57,249,427). TPRs were also identified in the T3S chaperone YscG from Yersinia spp., which binds together with its cochaperone YscE to the needle protein YscF (530) ( Table 4).…”

Section: Guides and Bodyguards-the T3s Chaperonesmentioning

confidence: 99%

Protein Export According to Schedule: Architecture, Assembly, and Regulation of Type III Secretion Systems from Plant- and Animal-Pathogenic Bacteria

Büttner

2012

Microbiol Mol Biol Rev

363

482

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SUMMARY Flagellar and translocation-associated type III secretion (T3S) systems are present in most Gram-negative plant- and animal-pathogenic bacteria and are often essential for bacterial motility or pathogenicity. The architectures of the complex membrane-spanning secretion apparatuses of both systems are similar, but they are associated with different extracellular appendages, including the flagellar hook and filament or the needle/pilus structures of translocation-associated T3S systems. The needle/pilus is connected to a bacterial translocon that is inserted into the host plasma membrane and mediates the transkingdom transport of bacterial effector proteins into eukaryotic cells. During the last 3 to 5 years, significant progress has been made in the characterization of membrane-associated core components and extracellular structures of T3S systems. Furthermore, transcriptional and posttranscriptional regulators that control T3S gene expression and substrate specificity have been described. Given the architecture of the T3S system, it is assumed that extracellular components of the secretion apparatus are secreted prior to effector proteins, suggesting that there is a hierarchy in T3S. The aim of this review is to summarize our current knowledge of T3S system components and associated control proteins from both plant- and animal-pathogenic bacteria.

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Bacterial secretins: Mechanisms of assembly and membrane targeting

et al. 2020

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Secretion systems are employed by bacteria to transport macromolecules across membranes without compromising their integrities. Processes including virulence, colonization, and motility are highly dependent on the secretion of effector molecules toward the immediate cellular environment, and in some cases, into the host cytoplasm. In Type II and Type III secretion systems, as well as in Type IV pili, homomultimeric complexes known as secretins form large pores in the outer bacterial membrane, and the localization and assembly of such 1 MDa molecules often relies on pilotins or accessory proteins. Significant progress has been made toward understanding details of interactions between secretins and their partner proteins using approaches ranging from bacterial genetics to cryo electron microscopy. This review provides an overview of the mode of action of pilotins and accessory proteins for T2SS, T3SS, and T4PS secretins, highlighting recent near‐atomic resolution cryo‐EM secretin complex structures and underlining the importance of these interactions for secretin functionality.

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Tetratricopeptide repeats are essential for PcrH chaperone function inPseudomonas aeruginosatype III secretion

Cited by 36 publications

References 42 publications

Structural Basis of Chaperone Recognition of Type III Secretion System Minor Translocator Proteins

Structural Basis of Chaperone Recognition of Type III Secretion System Minor Translocator Proteins

Protein Export According to Schedule: Architecture, Assembly, and Regulation of Type III Secretion Systems from Plant- and Animal-Pathogenic Bacteria

Bacterial secretins: Mechanisms of assembly and membrane targeting

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