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PDBsum entry 6hu8
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Transcription
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PDB id
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6hu8
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References listed in PDB file
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Key reference
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Title
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Molecular dissection of pheromone selectivity in the competence signaling system comrs of streptococci.
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Authors
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L.Ledesma-Garcia,
J.Thuillier,
A.Guzman-Espinola,
I.Ensinck,
I.Li de la sierra-Gallay,
N.Lazar,
M.Aumont-Nicaise,
J.Mignolet,
P.Soumillion,
S.Nessler,
P.Hols.
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Ref.
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Proc Natl Acad Sci U S A, 2020,
117,
7745-7754.
[DOI no: ]
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PubMed id
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Abstract
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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.
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