Structure and Mode of Peptide Binding of Pheromone Receptor PrgZ

Berntsson, R.P.-A.; Schuurman-Wolters, Gea K.; Dunny, Gary M.; Slotboom, Dirk Jan; Poolman, Bert

doi:10.1074/jbc.m112.386334

Cited by 21 publications

(25 citation statements)

References 35 publications

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“…This suggests that the functional competition between the two peptides occurs during PrgZ/Opp‐mediated import of the peptides. Recently, the structure of the secreted lipoprotein PrgZ and its complexes with I and C were analyzed (Berntsson, Schuurman‐Wolters, Dunny, Slotboom, & Poolman, ). The results indicate that PrgZ/ C complexes are more stable than PrgZ /I complexes.…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of peptide sex pheromone regulation of conjugation in Enterococcus faecalis

et al. 2017

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In many gram positive bacteria, horizontal transfer and virulence are regulated by peptide‐mediated cell‐cell signaling. The heptapeptide cCF10 (C) activates conjugative transfer of the Enterococcus faecalis plasmid pCF10, whereas the iCF10 (I) peptide inhibits transfer. Both peptides bind to the same domain of the master transcription regulator PrgX, a repressor of transcription of the prgQ operon encoding conjugation genes. We show that repression of prgQ by PrgX tetramers requires formation of a pCF10 DNA loop where each of two PrgX DNA‐binding sites is occupied by a dimer. I binding to PrgX enhances prgQ repression, while C binding has the opposite effect. Previous models suggested that differential effects of these two peptides on the PrgX oligomerization state accounted for their distinct functions. Our new results demonstrate that both peptides have similar, high‐binding affinity for PrgX, and that both peptides actually promote formation of PrgX tetramers with higher DNA‐binding affinity than Apo‐PrgX. We propose that differences in repression ability of PrgX/peptide complexes result from subtle differences in the structures of DNA‐bound PrgX/peptide complexes. Changes in the induction state of a donor cell likely results from replacement of one type of DNA‐bound peptide/PrgX tetramer with the other.

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Section: Discussionmentioning

confidence: 99%

Mechanisms of peptide sex pheromone regulation of conjugation in Enterococcus faecalis

et al. 2017

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“…These bonds are mostly formed with the peptide backbone, with one exception, an H-bond that is formed with the side chain of Thr3, giving an explanation for results from genetic screens that Thr3 of C was important for PrgZ binding (41). Further H-bonds between C and PrgZ are formed via bridging water molecules, and there is also a salt bridge that anchors the N terminus of C. Although no structure of PrgZ complexed with I is available, it is highly likely that I binds in the same way as C (37). This is expected due to the similarities of PrgZ to other oligopeptide-binding proteins (37,40,42,43).…”

Section: How and Why Did The Pcf10 System Become So Complex?mentioning

confidence: 99%

“…Previous experiments have shown that the oligopeptide-binding protein OppA of E. faecalis can facilitate the import of C, even though a higher concentration of C is required than is produced by recipients under normal physiological conditions (38). PrgZ can bind both C and I and has a typical Venus flytrap fold of a cluster C substratebinding protein (37), with C bound within an internal cavity (Fig. 3a).…”

Section: How and Why Did The Pcf10 System Become So Complex?mentioning

confidence: 99%

“…At the mechanistic level, the C peptide competes with I, which functions as a classic quorum-sensing signal of donor density (self-sensing) (64). Evolution of the ability to differentially respond to these two antagonistic peptides was accompanied by the acquisition of genes encoding an oligopeptide binding protein, PrgZ, which binds both C and I with high affinity and increases their import via the Opp ABC transporter (37,38), and PrgY, a predicted membrane peptidase that reduces the production of endogenous C by the host cell (36). III depicts the acquisition of T4SS and Dtr genes conferring conjugative transfer ability.…”

Section: Figmentioning

confidence: 99%

“…In the case of pCF10, the C peptide is produced by processing the cleaved signal peptide of a predicted secreted lipoprotein CcfA, whose function has not been demonstrated (15); likewise, all known pheromone-responsive plasmids analyzed to date encode a response to a specific peptide encoded by one of the Ͼ50 potential lipoprotein genes in the organism (16). As indicated in step II, the system acquired additional components that recognize C; PrgY prevents self-induction of donors by decreasing the amount of mature C released (36), and PrgZ binds both C and I and facilitates their import into the cell via a chromosomally encoded peptide transporter (37,38). PrgX also needed to evolve to recognize C and I.…”

Section: How and Why Did The Pcf10 System Become So Complex?mentioning

confidence: 99%

See 2 more Smart Citations

Enterococcal Sex Pheromones: Evolutionary Pathways to Complex, Two-Signal Systems

Dunny

Berntsson

2016

J Bacteriol

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bGram-positive bacteria carry out intercellular communication using secreted peptides. Important examples of this type of communication are the enterococcal sex pheromone systems, in which the transfer of conjugative plasmids is controlled by intercellular signaling among populations of donors and recipients. This review focuses on the pheromone response system of the conjugative plasmid pCF10. The peptide pheromones regulating pCF10 transfer act by modulating the ability of the PrgX transcription factor to repress the transcription of an operon encoding conjugation functions. Many Gram-positive bacteria regulate important processes, including the production of virulence factors, biofilm formation, sporulation, and genetic exchange using peptide-mediated signaling systems. The key master regulators of these systems comprise the RRNPP (RggRap/NprR/ PlcR/PrgX) family of intracellular peptide receptors; these regulators show conserved structures. While many RRNPP systems include a core module of two linked genes encoding the regulatory protein and its cognate signaling peptide, the enterococcal sex pheromone plasmids have evolved to a complex system that also recognizes a second host-encoded signaling peptide. Additional regulatory genes not found in most RRNPP systems also modulate signal production and signal import in the enterococcal pheromone plasmids. This review summarizes several structural studies that cumulatively demonstrate that the ability of three pCF10 regulatory proteins to recognize the same 7-amino-acid pheromone peptide arose by convergent evolution of unrelated proteins from different families. We also focus on the selective pressures and structure/function constraints that have driven the evolution of pCF10 from a simple, single-peptide system resembling current RRNPPs in other bacteria to the current complex inducible plasmid transfer system. BACKGROUND AND SIGNIFICANCE

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Identifying ligand-binding specificity of the oligopeptide receptor OppA from Bifidobacterium longum KACC91563 by structure-based molecular modeling

Chai

Ham²,

Lim³

2022

Arabian Journal of Chemistry

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Structure and Mode of Peptide Binding of Pheromone Receptor PrgZ

Cited by 21 publications

References 35 publications

Mechanisms of peptide sex pheromone regulation of conjugation in Enterococcus faecalis

Mechanisms of peptide sex pheromone regulation of conjugation in Enterococcus faecalis

Enterococcal Sex Pheromones: Evolutionary Pathways to Complex, Two-Signal Systems

Identifying ligand-binding specificity of the oligopeptide receptor OppA from Bifidobacterium longum KACC91563 by structure-based molecular modeling

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