TY  - JOUR
A1  - Hacker, Carolin
A1  - Christ, Nina A.
A1  - Duchardt-Ferner, Elke
A1  - Korn, Sophie
A1  - Göbl, Christoph
A1  - Berninger, Lucija
A1  - Düsterhus, Stefanie
A1  - Hellmich, Ute
A1  - Madl, Tobias
A1  - Kötter, Peter
A1  - Entian, Karl-Dieter
A1  - Wöhnert, Jens
T1  - The solution structure of the lantibiotic immunity protein NisI and its interactions with nisin
T2  - Journal of biological chemistry
N2  - 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.
KW  - antibiotic resistance
KW  - antibiotics
KW  - lipoprotein
KW  - nuclear magnetic resonance (NMR)
KW  - protein structure
KW  - lantibiotic
KW  - nisin binding
KW  - small angle x-ray scattering
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/77207
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-772074
SN  - 0021-9258
VL  - 290.2015
IS  - 48
SP  - 28869
EP  - 28886
PB  - American Society for Biochemistry and Molecular Biology Publications
CY  - Bethesda, Md
ER  -