The structure of pyogenecin immunity protein, a novel bacteriocin-like immunity protein from Streptococcus pyogenes

We have solved the crystal structure of the gene-product of locus Spy_2152 from S. pyogenes, (PDB:2fu2), and found it to comprise an anti-parallel four-helix bundle that is structurally similar to other bacteriocin immunity proteins. Sequence analyses indicate this protein to be a possible immunity protein protective against class IIa or IIb bacteriocins. However, given that S. pyogenes appears to lack any IIa pediocin-like proteins but does possess class IIb bacteriocins, we suggest this protein confers immunity to IIb-like peptides.Combined structural, genomic and proteomic analyses have allowed the identification and in silico characterization of a new putative immunity protein from S. pyogenes, possibly the first structure of an immunity protein protective against potential class IIb two-peptide bacteriocins. We have named the two pairs of putative bacteriocins found in S. pyogenes pyogenecin 1, 2, 3 and 4.Many Gram-positive bacteria produce anti-bacterial peptides and small proteins, called bacteriocins. There are three main classes produced by Gram-positive lactic acid bacteria (LAB): class I bacteriocins are the lantibiotics, small (<4 kDa), post-translationally modified peptides containing unusual amino acids such as lanthionine; class II are small, unmodified, heat-stable bacteriocins (<10 kDa); class III include larger (>30 kDa) heat-labile proteins, such as murein hydrolases [1]. Most bacteriocins are synthesized as precursors, which are matured and secreted, then target a specific bacterium and kill it by increasing its membrane permeability to various small molecules. Class II bacteriocins are subdivided into IIa, pediocin-like unmodified bacteriocins, IIb, two-peptide unmodified bacteriocins, IIc, formerly class V, where the N- and C-termini are covalently linked resulting in a cyclic structure, and class IId, non-pediocin, single, linear peptides [2]. The genetics and biosynthesis of class IIa bacteriocins have been well studied [3], and these constit