Structure-activity analysis of quorum-sensing signaling peptides from Streptococcus mutans
Date
2007-02
Authors
Syvitski, Raymond T.
Tian, Xiao-Lin
Sampara, Kamal
Salman, Alan
Lee, Song F.
Jakeman, David L.
Li, Yung-Hua
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Abstract
Streptococcus mutans secretes and utilizes a 21-amino-acid signaling peptide pheromone to
initiate quorum sensing for genetic competence, biofilm formation, stress responses, and bacteriocin
production. In this study, we designed and synthesized a series of truncated peptides and peptides
with amino acid substitutions to investigate their structure-activity relationships based on the
three-dimensional structures of S. mutans wild-type signaling peptide UA159sp and C-terminally
truncated peptide TPC3 from mutant JH1005 defective in genetic competence. By analyzing these
peptides, we demonstrated that the signaling peptide of S. mutans has at least two functional
domains. The C-terminal structural motif consisting of a sequence of polar hydrophobic charged
residues is crucial for activation of the signal transduction pathway, while the core a-helical
structure extending from residue 5 to the end of the peptide is required for receptor binding.
Peptides in which three or more residues were deleted from the C terminus did not induce genetic
competence but competitively inhibited quorum sensing activated by UA159sp. Disruption of the
amphipathic a-helix by replacing the Phe-7, Phe-11, or Phe-15 residue with a hydrophilic residue
resulted in a significant reduction in or complete loss of the activity of the peptide. In contrast
to the C-terminally truncated peptides, these peptides with amino acid substitutions did not compete
with UA159sp to activate quorum sensing, suggesting that disruption of the hydrophobic face of the
a-helical structure results in a peptide that is not able to bind to the receptor. This study is the
first study to recognize the importance of the signaling peptide C-terminal residues in
streptococcal quorum sensing.
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Citation
Syvitski, Raymond T., Xiao-Lin Tian, Kamal Sampara, Alan Salman, et al. 2007. "Structure-activity analysis of quorum-sensing signaling peptides from Streptococcus mutans." Journal of Bacteriology 189(4): 1441-1450.