Binding of MgtR, a Salmonella transmembrane regulatory peptide, to MgtC, a Mycobacterium tuberculosis virulence factor: a structural study

J Mol Biol. 2014 Jan 23;426(2):436-46. doi: 10.1016/j.jmb.2013.10.014. Epub 2013 Oct 17.


MgtR, a highly hydrophobic peptide expressed in Salmonella enterica serovar Typhimurium, inhibits growth in macrophages through binding to the membrane protein MgtC that has been identified as essential for replication in macrophages. While the Mycobacterium tuberculosis MgtC is highly homologous to its S. Typhi analogue, there does not appear to be an Mtb homologue for MgtR, raising significant pharmacological interest in this system. Here, solid-state NMR and EPR spectroscopy in lipid bilayer preparations were used to demonstrate the formation of a heterodimer between S. Typhi MgtR and the transmembrane helix 4 of Mtb MgtC. Based on the experimental restraints, a structural model of this heterodimer was developed using computational techniques. The result is that MgtR appears to be ideally situated in the membrane to influence the functionality of MgtC.

Keywords: MD; PISEMA; distance restraints; electron spin resonance; molecular dynamics; orientational restraints; polarization inversion spin exchange at the magic angle; restrained molecular dynamics; solid-state nuclear magnetic resonance.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism*
  • Electron Spin Resonance Spectroscopy
  • Lipid Bilayers / chemistry
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Mycobacterium tuberculosis / metabolism*
  • Protein Binding
  • Protein Conformation
  • Protein Interaction Mapping*
  • Protein Multimerization*
  • Salmonella typhimurium / metabolism*


  • Bacterial Proteins
  • Lipid Bilayers

Associated data

  • PDB/2MC7