Molecular dissection of pheromone selectivity in the competence signaling system ComRS of streptococci
| Autor: | Noureddine Lazar, Sylvie Nessler, Laura Ledesma-Garcia, Magali Aumont-Nicaise, Inès Li de la Sierra-Gallay, Imke Ensinck, Johann Mignolet, Armando Guzman-Espinola, Pascal Hols, Patrice Soumillion, Jordhan Thuillier |
|---|---|
| Přispěvatelé: | Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Fonction et Architecture des Assemblages Macromoléculaires (FAAM), Département Biochimie, Biophysique et Biologie Structurale (B3S), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Mesures d'interactions protéine-protéine (PIM), Département Plateforme (PF I2BC), UCL - SST/LIBST - Louvain Institute of Biomolecular Science and Technology, University Paris-Sarclay - Institute of Integrative Biology of the Cell (I2BC) |
| Rok vydání: | 2020 |
| Předmět: |
Models
Molecular [SDV]Life Sciences [q-bio] Mutant Peptide binding Biology medicine.disease_cause Pheromones Protein Structure Secondary 03 medical and health sciences XIP pheromone medicine Point Mutation Amino Acid Sequence Luciferases 030304 developmental biology Genetics 0303 health sciences Mutation Multidisciplinary 030306 microbiology Point mutation cell-to-cell communication Rational design quorum sensing Streptococcus Biological Sciences Directed evolution Quorum sensing (R)RNPP Structural Homology Protein Neofunctionalization cross-talk Signal Transduction |
| Zdroj: | Proc Natl Acad Sci U S A Proceedings of the National Academy of Sciences of the United States of America Proceedings of the National Academy of Sciences of the United States of America, National Academy of Sciences, 2020, ⟨10.1073/pnas.1916085117⟩ Proceedings of the National Academy of Sciences of the United States of America, 2020, ⟨10.1073/pnas.1916085117⟩ Proceedings of the National Academy of Sciences, Vol. 117, no.14, p. 201916085 (2020) |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1916085117 |
| Popis: | Competence allows bacteria to internalize exogenous DNA fragments for the acquisition of new phenotypes such as antibiotic resistance or virulence traits. In most streptococci, competence is regulated by ComRS signaling, a system based on the mature ComS pheromone (XIP), which is internalized to activate the (R)RNPP-type ComR sensor by triggering dimerization and DNA binding. Cross-talk analyses demonstrated major differences of selectivity between ComRS systems and raised questions concerning the mechanism of pheromone-sensor recognition and coevolution. Here, we decipher the molecular determinants of selectivity of the closely related ComRS systems from Streptococcus thermophilus and Streptococcus vestibularis . Despite high similarity, we show that the divergence in ComR-XIP interaction does not allow reciprocal activation. We perform the structural analysis of the ComRS system from S. vestibularis. Comparison with its ortholog from S. thermophilus reveals an activation mechanism based on a toggle switch involving the recruitment of a key loop by the XIP C terminus. Together with a broad mutational analysis, we identify essential residues directly involved in peptide binding. Notably, we generate a ComR mutant that displays a fully reversed selectivity toward the heterologous pheromone with only five point mutations, as well as other ComR variants featuring XIP bispecificity and/or neofunctionalization for hybrid XIP peptides. We also reveal that a single XIP mutation relaxes the strictness of ComR activation, suggesting fast adaptability of molecular communication phenotypes. Overall, this study is paving the way toward the rational design or directed evolution of artificial ComRS systems for a range of biotechnological and biomedical applications. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|