Structural Insights into Streptococcal Competence Regulation by the Cell-to-Cell Communication System ComRS

Talagas, Antoine; Fontaine, Laetitia; Laura, Ledesma-Garca; Mignolet, Johann; Sierra-Gallay, I. Li de la; Lazar, Noureddine; Aumont-Niçaise, Magali; Federle, Michael J.; Prehna, Gerd; Hols, Pascal; Nessler, Sylvie

doi:10.1371/journal.ppat.1005980

Cited by 53 publications

(116 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…thermophilus structure (Talagas, et al . [37]) the lower end of the pocket does not interact with the bound peptide, including residue K260 on the conserved face that is strictly conserved in all ComR strains used in our study (Fig 5, Fig 6B, S5A and S5B Fig). This could suggest a different mode of interaction with XIP, possibly in a more extended conformation, or that K260 performs an accessory role such as help to orient the CAP helix given that it forms a salt-bridge with D302 (Fig 6).…”

Section: Resultsmentioning

confidence: 83%

“…Given this, we hypothesize that this may mimic in part an initial peptide interaction event that occurs when the XIP binding pocket is in the apo conformation. If the interacting XIP is accepted it can then trigger the conformational change of the TPR domain to open the DBD-TPR interface to allow dimer formation and activation as proposed by Talagas, et al (Fig 7 and S5 Fig) [37]. …”

Section: Resultsmentioning

confidence: 99%

“…al. [37]), and the variable face (N220A) (Fig 5, S5B Fig and Fig 8A). These variants were placed into the ES1 test-bed background, and luciferase activity was recorded after stimulation with the S .…”

Section: Resultsmentioning

confidence: 99%

“…al. [37]). The loss in activity could result from either disruption of the regulator mechanism or reduced affinity for DNA.…”

Section: Resultsmentioning

confidence: 99%

See 3 more Smart Citations

Pheromone Recognition and Selectivity by ComR Proteins among Streptococcus Species

Shanker¹,

Morrison²,

Talagas³

et al. 2016

PLoS Pathog

Self Cite

107

View full text Add to dashboard Cite

Natural transformation, or competence, is an ability inherent to bacteria for the uptake of extracellular DNA. This process is central to bacterial evolution and allows for the rapid acquirement of new traits, such as antibiotic resistance in pathogenic microorganisms. For the Gram-positive bacteria genus Streptococcus, genes required for competence are under the regulation of quorum sensing (QS) mediated by peptide pheromones. One such system, ComRS, consists of a peptide (ComS) that is processed (XIP), secreted, and later imported into the cytoplasm, where it binds and activates the transcription factor ComR. ComR then engages in a positive feedback loop for the expression of ComS and the alternative sigma-factor SigX. Although ComRS are present in the majority of Streptococcus species, the sequence of both ComS/XIP and ComR diverge significantly, suggesting a mechanism for species-specific communication. To study possible cross-talk between streptococcal species in the regulation of competence, and to explore in detail the molecular interaction between ComR and XIP we undertook an interdisciplinary approach. We developed a ‘test-bed’ assay to measure the activity of different ComR proteins in response to cognate and heterologous XIP peptides in vivo, revealing distinct ComR classes of strict, intermediate, and promiscuous specificity among species. We then solved an X-ray crystal structure of ComR from S. suis to further understand the interaction with XIP and to search for structural features in ComR proteins that may explain XIP recognition. Using the structure as a guide, we probed the apo conformation of the XIP-binding pocket by site-directed mutagenesis, both in test-bed cultures and biochemically in vitro. In alignments with ComR proteins from other species, we find that the pocket is lined by a variable and a conserved face, where residues of the conserved face contribute to ligand binding and the variable face discriminate among XIP peptides. Together, our results not only provide a model for XIP recognition and specificity, but also allow for the prediction of novel XIP peptides that induce ComR activity.

show abstract

Section: Resultsmentioning

confidence: 83%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

“…al. [37]). The loss in activity could result from either disruption of the regulator mechanism or reduced affinity for DNA.…”

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

Pheromone Recognition and Selectivity by ComR Proteins among Streptococcus Species

Shanker¹,

Morrison²,

Talagas³

et al. 2016

PLoS Pathog

Self Cite

107

View full text Add to dashboard Cite

show abstract

“…64 Curiosamente o N-terminal deste RT apenas se cruza (domain swap) para / ou após se ligar no DNA. [65][66] Representantes …”

Section: Sistemas Qs Descritos Para Gram Positivosunclassified

Estudos cristalográficos da proteína ElrR, regulador transcricional do fator de virulência ElrA de <i>Enterococcus faecalis</i>, e indícios de sua interação com a região de ligação ao DNA

Groote¹

View full text Add to dashboard Cite

Ultrashort‐Peptide‐Responsive Gene Switches for Regulation of Therapeutic Protein Expression in Mammalian Cells

Huang,

Xue,

Xie

et al. 2024

Advanced Science

View full text Add to dashboard Cite

Despite the array of mammalian transgene switches available for regulating therapeutic protein expression in response to small molecules or physical stimuli, issues remain, including cytotoxicity of chemical inducers and limited biocompatibility of physical cues. This study introduces gene switches driven by short peptides comprising eight or fewer amino acid residues. Utilizing a competence regulator (ComR) and sigma factor X‐inducing peptide (XIP) from Streptococcus vestibularis as the receptor and inducer, respectively, this study develops two strategies for a peptide‐activated transgene control system. The first strategy involves fusing ComR with a transactivation domain and utilizes ComR‐dependent synthetic promoters to drive expression of the gene‐of‐interest, activated by XIP, thereby confirming its membrane penetrability and intracellular functionality. The second strategy features an orthogonal synthetic receptor exposing ComR extracellularly (ComREXTRA), greatly increasing sensitivity with exceptional responsiveness to short peptides. In a proof‐of‐concept study, peptides are administered to type‐1 diabetic mice with microencapsulated engineered human cells expressing ComREXTRA for control of insulin expression, restoring normoglycemia. It is envisioned that this system will encourage the development of short peptide drugs and promote the introduction of non‐toxic, orthogonal, and highly biocompatible personalized biopharmaceuticals for gene‐ and cell‐based therapies.

show abstract

Structural Insights into Streptococcal Competence Regulation by the Cell-to-Cell Communication System ComRS

Cited by 53 publications

References 67 publications

Pheromone Recognition and Selectivity by ComR Proteins among Streptococcus Species

Pheromone Recognition and Selectivity by ComR Proteins among Streptococcus Species

Estudos cristalográficos da proteína ElrR, regulador transcricional do fator de virulência ElrA de <i>Enterococcus faecalis</i>, e indícios de sua interação com a região de ligação ao DNA

Ultrashort‐Peptide‐Responsive Gene Switches for Regulation of Therapeutic Protein Expression in Mammalian Cells

Contact Info

Product

Resources

About