2i2h

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2i2h

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NMR structure of TPC3 in TFE

Overview

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, alpha-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 alpha-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 alpha-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.

About this Structure

2I2H is a Protein complex structure of sequences from [1] with as ligand. Full crystallographic information is available from OCA.

Reference

Structure-activity analysis of quorum-sensing signaling peptides from Streptococcus mutans., Syvitski RT, Tian XL, Sampara K, Salman A, Lee SF, Jakeman DL, Li YH, J Bacteriol. 2007 Feb;189(4):1441-50. Epub 2006 Aug 25. PMID:16936029

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