Project Details
Projekt
Specificity, structure and function of the lantibiotic immunity proteins SpaI and NisI
Subject Area
Structural Biology
Term
from 2013 to 2017
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 240920551
Lantibiotics are peptide antibiotics containing characteristic lanthionine ring structures. They are ribosomally synthesized and post-translationally modified. The antibiotic mode of action of lantibiotics subtilin from Bacillus subtilis and ninin from Lactococcus lactis are based on the binding to the cell wall precursor lipid II and the formation of multimere lantibiotic/lipid II membrane complexes. Lantibiotic producers are sensitive against their own lantibiotic and therefore they express a membrane bound LanI immunity protein and an independent ABC-transporter complex. The mode of action and the molecular mechanism of LanI mediated immunity are still unknown. Although subtilin and nisin have a similar molecular structure, the respective immunity proteins NisI and SpaI are highly selective for the respective antibiotic. We could resolve the NMR-structure of SpaI in solution, with a so far unknown folding pattern. No conclusions on the immunity mechanism could be drawn form the structure so far. At present we consider four possible mechanisms for SpaI mediated immunity, which we want to verify during the project: (A) LanI proteins capture lantibiotics before they reach the cytoplasma membrane (capture function), (B) LanI proteins interact with lantibiotic/lipid II pores to prevent pore formation (complex inhibition), (C) LanI interact and destroy existing lantibiotic/lipid II pores (pore destruction), and (D) SpaI protein seal existing lantibiotic/lipid II pores (pore sealing). Aim of the project is to understand the molecular mechanisms, the high specificity and the membrane interaction of SpaI and NisI proteins by comparing the functional homologue and structural most likely different immunity proteins, using molecular biological, biochemical and biopyhysical methods. Understanding the molecular mechanism and the specificity of SpaI immunity is also important for a possible application of nisin and subtilin variants with altered antibiotic activities.
DFG Programme
Research Grants
