Tetratricopeptide Repeat Motifs in the World of Bacterial Pathogens: Role in Virulence Mechanisms

Červený, Lukáš; Strašková, Adéla; Daňková, Věra; Härtlová, Anetta; Čečková, Martina; Štaud, František; Stulı́k, Jiřı́

doi:10.1128/iai.01035-12

Cited by 184 publications

(161 citation statements)

References 76 publications

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“…Indeed, the occurrence of TPR in the FCBPs, but not in the CFBPs, parallels the greater prevalence of the TPR domains in eukaryotes over prokaryotes (Cerveny et al 2013).…”

Section: Modular and Unique Domain Arrangements Of The Dfismentioning

confidence: 99%

“…Unique TPR signature of the FCBP family and its phylogenetic subsets TPR sequences are roughly 34 amino acid-long, degenerate repeats, in which the properties of key amino acids in specific positions, rather than the exact residues, are conserved (Cerveny et al 2013;D'Andrea and Regan 2003). Although TPRs occur in various number of repeats, a recent large-scale survey of all TPR-containing proteins in living organisms revealed that three-TPR (3TPR) is the most common, comprising~40% of all TPRs (Sawyer et al 2013).…”

Section: Gammaproteobacteriamentioning

confidence: 99%

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On the role, ecology, phylogeny, and structure of dual-family immunophilins

Barik¹

2017

Cell Stress and Chaperones

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The novel class of dual-family immunophilins (henceforth abbreviated as DFI) represents naturally occurring chimera of classical FK506-binding protein (FKBP) and cyclophilin (CYN), connected by a flexible linker that may include a three-unit tetratricopeptide (TPR) repeat. Here, I report a comprehensive analysis of all current DFI sequences and their host organisms. DFIs are of two kinds: CFBP (cyclosporin-and FK506-binding protein) and FCBP (FK506-and cyclosporin-binding protein), found in eukaryotes. The CFBP type occurs in select bacteria that are mostly extremophiles, such as psychrophilic, thermophilic, halophilic, and sulfur-reducing. Essentially all DFI organisms are unicellular. I suggest that DFIs are specialized bifunctional chaperones that use their flexible interdomain linker to associate with large polypeptides or multisubunit megacomplexes to promote simultaneous folding or renaturation of two clients in proximity, essential in stressful and denaturing environments. Analysis of sequence homology and predicted 3D structures of the FKBP and CYN domains as well as the TPR linkers upheld the modular nature of the DFIs and revealed the uniqueness of their TPR domain. The CFBP and FCBP genes appear to have evolved in parallel pathways with no obvious single common ancestor. The occurrence of both types of DFI in multiple unrelated phylogenetic clades supported their selection in metabolic and environmental niche roles rather than a traditional taxonomic relationship.Nonetheless, organisms with these rare immunophilins may define an operational taxonomic unit (OTU) bound by the commonality of chaperone function.

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“…Indeed, the occurrence of TPR in the FCBPs, but not in the CFBPs, parallels the greater prevalence of the TPR domains in eukaryotes over prokaryotes (Cerveny et al 2013).…”

Section: Modular and Unique Domain Arrangements Of The Dfismentioning

confidence: 99%

Section: Gammaproteobacteriamentioning

confidence: 99%

On the role, ecology, phylogeny, and structure of dual-family immunophilins

Barik¹

2017

Cell Stress and Chaperones

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“…Both ANKs and TPRs mediate protein-protein interactions and are known as eukaryote-like proteins (ELPs), in reference to their identification first in eukaryote genomes, but more recently also in many prokaryote genomes. TPRcontaining proteins are known to play critical roles as bacterial virulence factors (Cerveny et al, 2013), and their presence in the genome of a sponge Pseudovibrio sp. symbiont has been postulated to aid in attachment to the eukaryotic host and in avoidance of the host's immune response (Alex and Antunes, 2015).…”

Section: Differential Expression Analysis Of Sponge Genes Indicates Smentioning

confidence: 99%

Ontogenetic Changes in the Bacterial Symbiont Community of the Tropical Demosponge Amphimedon queenslandica: Metamorphosis Is a New Beginning

et al. 2016

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Vertical transmission of bacterial symbionts, which is known in many species of sponge (Porifera), is expected to promote strong fidelity between the partners. Combining 16S rRNA gene amplicon sequencing and electron microscopy, we have assayed the relative abundance of vertically-inherited bacterial symbionts in several stages of the life cycle of Amphimedon queenslandica, a tropical coral reef sponge. We reveal that adult A. queenslandica house a low diversity microbiome dominated by just three proteobacterial OTUs, with a single gammaprotebacterium clearly dominant through much of the life cycle. This ontogenetic perspective has revealed that, although vertical transmission occurs very early in development, the inherited symbionts do not maintain proportional dominance of the bacterial community at every developmental stage. A reproductive bottleneck in the A. queenslandica life cycle is larval settlement, when a free-swimming pelagic larva settles out of the water column onto the benthos and completes metamorphoses into the sessile body plan within just 3-4 days. During this dramatic life cycle transition, an influx of environmentally-derived bacteria leads to a major reorganization of the microbiome, potentially challenging the fidelity and persistence of the vertically-inherited symbiotic relationships. However, dominance of the primary, vertically-inherited symbionts is restored in adult sponges. The mechanisms underlying ontogenetic changes in the bacterial community are unknown, including how the dominance of the primary symbionts is restored in the adult sponge-does the host or symbiont regulate this process? Using high-resolution transcriptional profiling in multiple stages of the A. queenslandica life cycle combined with this natural perturbation of the microbiome immediately following larval settlement, we are beginning to identify candidate host genes associated with animal-bacterial crosstalk. Among the sponge host genes upregulated during the times of active microbiome assembly, there is an enrichment of genes potentially involved in innate immunity, including scavenger receptors, and of genes containing eukaryote-like domains, which have elsewhere Fieth et al.Sponge Microbiome Changes through Lifecycle been implicated in host-symbiont interactions. Intriguingly, we also see an enrichment of sponge genes arising from ancient horizontal transfer events from bacteria, which raises the possibility that host-bacterial associations in the evolutionary past may help to regulate host-bacterial associations in the ecological present.

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“…TPR protein sequences are highly variable, although a core consensus sequence, W 4 -L 7 -G 8 -Y 11 -A 20 -F 24 -A 27 -P 32 , was identified two decades ago (24). None of the positions of the consensus are invariable, although hydrophobic residues are commonly observed at those positions (24)(25)(26). Of the three predicted TPR motifs in P. aeruginosa FimV, two are organized in tandem, proximal to the inner membrane (TPR1 and TPR2, residues 544 to 611), while the third (TPR3, residues 873 to 906) is at the C terminus, separated from TPR1 and TPR2 by a long, highly acidic region predicted to lack a regular secondary structure (17).…”

mentioning

confidence: 99%

The Conserved Tetratricopeptide Repeat-Containing C-Terminal Domain of Pseudomonas aeruginosa FimV Is Required for Its Cyclic AMP-Dependent and -Independent Functions

et al. 2016

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FimV is a Pseudomonas aeruginosa inner membrane protein that regulates intracellular cyclic AMP (cAMP) levels-and thus type IV pilus (T4P)-mediated twitching motility and type II secretion (T2S)-by activating the adenylate cyclase CyaB. Its cytoplasmic domain contains three predicted tetratricopeptide repeat (TPR) motifs separated by an unstructured region: two proximal to the inner membrane and one within the "FimV C-terminal domain," which is highly conserved across diverse homologs. Here, we present the crystal structure of the FimV C terminus, FimV 861-919 , containing a TPR motif decorated with solvent-exposed, charged side chains, plus a C-terminal capping helix. FimV 689 , a truncated form lacking this C-terminal motif, did not restore wild-type levels of twitching or surface piliation compared to the full-length protein. FimV 689 failed to restore wild-type levels of the T4P motor ATPase PilU or T2S, suggesting that it was unable to activate cAMP synthesis. Bacterial two-hybrid analysis showed that TPR3 interacts directly with the CyaB activator, FimL. However, FimV 689 failed to restore wild-type motility in a fimV mutant expressing a constitutively active CyaB (fimV cyaB-R456L), suggesting that the C-terminal motif is also involved in cAMP-independent functions of FimV. The data show that the highly conserved TPR-containing C-terminal domain of FimV is critical for its cAMP-dependent and -independent functions. IMPORTANCEFimV is important for twitching motility and cAMP-dependent virulence gene expression in P. aeruginosa. FimV homologs have been identified in several human pathogens, and their functions are not limited to T4P expression. The C terminus of FimV is remarkably conserved among otherwise very diverse family members, but its role is unknown. We provide here biological evidence for the importance of the C-terminal domain in both cAMP-dependent (through FimL) and -independent functions of FimV. We present X-ray crystal structures of the conserved C-terminal domain and identify a consensus sequence for the C-terminal TPR within the conserved domain. Our data extend our knowledge of FimV's functionally important domains, and the structures and consensus sequences provide a foundation for studies of FimV and its homologs. T ype IV pili (T4P) are filamentous surface appendages produced by a wide range of bacteria and archaea (1, 2), where they assist in DNA uptake, surface attachment, and twitching motility (3-5). There are two major subfamilies of T4P: T4aP and T4bP. T4aP are typically associated with twitching (2), a process in which pili undergo repeated cycles of extension, adhesion, and retraction, thus acting as molecular grappling hooks to pull cells along a surface.The T4aP machinery is composed of four structural subcomplexes (6). In the model bacterium Pseudomonas aeruginosa, an inner membrane motor subcomplex consisting of the platform protein PilC and three hexameric ATPases-PilB, PilT, and PilU-provide energy for T4aP extension and retraction (7-9). A second inner membrane al...

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Tetratricopeptide Repeat Motifs in the World of Bacterial Pathogens: Role in Virulence Mechanisms

Cited by 184 publications

References 76 publications

On the role, ecology, phylogeny, and structure of dual-family immunophilins

On the role, ecology, phylogeny, and structure of dual-family immunophilins

Ontogenetic Changes in the Bacterial Symbiont Community of the Tropical Demosponge Amphimedon queenslandica: Metamorphosis Is a New Beginning

The Conserved Tetratricopeptide Repeat-Containing C-Terminal Domain of Pseudomonas aeruginosa FimV Is Required for Its Cyclic AMP-Dependent and -Independent Functions

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