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J Biol Chem. 2015 Nov 27;290(48):28869-86. doi: 10.1074/jbc.M115.679969. Epub 2015 Oct 12.

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

Author information

1
From the Institute for Molecular Biosciences and the Center of Biomolecular Magnetic Resonance (BMRZ), Goethe University, 60438 Frankfurt am Main, Germany.
2
From the Institute for Molecular Biosciences and.
3
the Department of Chemistry, Center for Integrated Protein Science Munich, Technical University München, Lichtenbergstraße 4, 85748 Garching, Germany, the Institute of Structural Biology, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
4
the Center of Biomolecular Magnetic Resonance (BMRZ), Goethe University, 60438 Frankfurt am Main, Germany, the Institute of Pharmacy and Biochemistry, Gutenberg University, 55128 Mainz, Germany.
5
the Department of Chemistry, Center for Integrated Protein Science Munich, Technical University München, Lichtenbergstraße 4, 85748 Garching, Germany, the Institute of Structural Biology, Helmholtz Zentrum München, 85764 Neuherberg, Germany, the Institute of Molecular Biology & Biochemistry, Center of Molecular Medicine, Medical University of Graz, 8010 Graz, Austria, and the Omics Center Graz, BioTechMed Graz, 8010 Graz, Austria.
6
From the Institute for Molecular Biosciences and the Center of Biomolecular Magnetic Resonance (BMRZ), Goethe University, 60438 Frankfurt am Main, Germany, woehnert@bio.uni-frankfurt.de.

Abstract

Many Gram-positive bacteria produce lantibiotics, genetically encoded and posttranslationally modified peptide antibiotics, which inhibit the growth of other Gram-positive bacteria. To protect themselves against their own lantibiotics these bacteria express a variety of immunity proteins including the LanI lipoproteins. The structural and mechanistic basis for LanI-mediated lantibiotic immunity is not yet understood. Lactococcus lactis produces the lantibiotic nisin, which is widely used as a food preservative. Its LanI protein NisI provides immunity against nisin but not against structurally very similar lantibiotics from other species such as subtilin from Bacillus subtilis. To understand the structural basis for LanI-mediated immunity and their specificity we investigated the structure of NisI. We found that NisI is a two-domain protein. Surprisingly, each of the two NisI domains has the same structure as the LanI protein from B. subtilis, SpaI, despite the lack of significant sequence homology. The two NisI domains and SpaI differ strongly in their surface properties and function. Additionally, SpaI-mediated lantibiotic immunity depends on the presence of a basic unstructured N-terminal region that tethers SpaI to the membrane. Such a region is absent from NisI. Instead, the N-terminal domain of NisI interacts with membranes but not with nisin. In contrast, the C-terminal domain specifically binds nisin and modulates the membrane affinity of the N-terminal domain. Thus, our results reveal an unexpected structural relationship between NisI and SpaI and shed light on the structural basis for LanI mediated lantibiotic immunity.

KEYWORDS:

antibiotic resistance; antibiotics; lantibiotic; lipoprotein; nisin binding; nuclear magnetic resonance (NMR); protein structure; small angle x-ray scattering

PMID:
26459561
PMCID:
PMC4661402
DOI:
10.1074/jbc.M115.679969
[Indexed for MEDLINE]
Free PMC Article

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