Heterooligomerization of Membrane Peptides Involved in Tuberculosis: MgtC and MgtR
Recent results have converged to highlight the role of hydrophobic peptides that form a novel class of active molecules in Escherichia coli and Salmonella enterica serovar Typhimurium. These peptides are apparently able to interact with membrane proteins leading to their inactivation through an unfolding process. MgtR, a highly hydrophobic 30 amino acid peptide, expressed in Salmonella typhimurium is one of these inactivating molecules. It has been shown that within the macrophage, the interaction between MgtR and the membrane protein MgtC leads to a decrease of Salmonella replication rate. This phenomenon can be explained by the importance of MgtC for the survival of the bacterium at low magnesium concentrations.To our knowledge, an interaction between two different peptides (heterooligomer) has never been studied in a membrane environment by NMR. Relying on the sequence homology between Salmonella typhimurium MgtC and Mycobacterium tuberculosis MgtC, the interaction between MgtR from Salmonella typhimurium and the transmembrane helix #4 of Mycobacterium tuberculosis MgtC is studied.Beyond the challenge consisting of solving a membrane protein structure, Solid state NMR and EPR are two powerful techniques to decipher protein dynamics and structure within the membrane hydrophobic core. Understanding the molecular mechanism of these peptide-protein interactions would offer great opportunities in pharmacology and drug design.Structural studies using solid state NMR spectroscopy of liposomal preparations for magic angle spinning experiments and oriented bilayer samples for additional structural restraints have been performed. EPR distance measurements were also performed on theses peptides in the membrane environment. The use of the NMR and EPR restrains combined, allowed us to propose a hypothetical interaction between these peptides in the membrane core.