The First Structure of a Lantibiotic Immunity Protein, SpaI from Bacillus subtilis, Reveals a Novel Fold

Abstract

Background:The periplasmic lipoprotein SpaI protects the subtilin-producing Bacillus subtilis against its own lantibiotic by an unknown mechanism. Results: The first structure of a lantibiotic immunity protein, SpaI, reveals a novel fold and its membrane-interacting regions. Conclusion:The membrane interaction is important for SpaI-mediated immunity. Significance: The SpaI structure will help to understand the immunity of B. subtilis against subtilin on a structural level.

The Solution Structure of the Lantibiotic Immunity Protein NisI and Its Interactions with Nisin

“…Furthermore, NisI only confers immunity against nisin, whereas SpaI is only active against subtilin and both proteins are not able to confer cross-immunity against the other lantibiotic (24). The structure of SpaI revealed a long, disordered, positively charged N terminus able to interact with membranes and a structured core domain with a central six-stranded ␤-sheet establishing a novel three-dimensional fold class (22). Our solution NMR studies of NisI demonstrate that NisI is a two-domain protein.…”

“…For SpaI it was shown that the unstructured basic N terminus is able to bind to membranes even in the absence of a lipid anchor (22). NisI does not contain an unstructured N terminus like SpaI but an N-terminal domain with a highly positively charged surface.…”

“…NisI does not contain an unstructured N terminus like SpaI but an N-terminal domain with a highly positively charged surface. To test if NisI is able to interact with membranes even in the absence of a covalent diacylglycerol anchor the interaction of NisI with liposomes composed of the two major phospholipids found in L. lactis 1,2-dioleoyl-snglycero-3-phospho-(1-rac-glycerol) and cardiolipin in an 1:3 molar ratio (22) was investigated. Both phospholipids harbor a negatively charged head group, which might interact with residues of the positively charged surface of the NisI N-terminal domain.…”

“…Structural insights into the organization of LanI proteins are so far limited to the solution structure of SpaI (22), which protects B. subtilis against the lantibiotic subtilin. Although nisin and subtilin are structurally very similar the two LanI proteins differ significantly in size and only very limited sequence homology was observed.…”

“…Structural information for lantibiotic immunity proteins in general and LanI proteins in particular is so far very limited. Only a solution structure for a LanI protein has been solved (22) so far, the structure of SpaI from Bacillus subtilis conferring immunity against subtilin. In addition, the structure for the unrelated lipoprotein MlbQ conferring immunity to actinomycetes against NAI-107 has been reported (23).…”