title: Binding of MgtR, a Salmonella transmembrane regulatory peptide, to MgtC, a Mycobacterium tuberculosis virulence factor: a structural study.
abstract: 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.
authors.affiliation: National High Magnetic Field Laboratory, Tallahassee, FL 32306, USA; Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL 32306, USA.
authors.forename: Frantz L
authors.initials: FL
authors.lastname: Jean-Francois
authors.affiliation: Department of Physics, Florida State University, Tallahassee, FL 32306, USA; Institute of Molecular Biophysics, Florida State University, Tallahassee, FL 32306, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Dai
authors.affiliation: University of Science and Technology of China, Hefei 230031, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02138, USA.
authors.forename: Alissa
authors.initials: A
authors.lastname: Myrick
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02138, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Rubin
authors.affiliation: National High Magnetic Field Laboratory, Tallahassee, FL 32306, USA; Institute of Molecular Biophysics, Florida State University, Tallahassee, FL 32306, USA.
authors.forename: Piotr G
authors.initials: PG
authors.lastname: Fajer
authors.affiliation: National High Magnetic Field Laboratory, Tallahassee, FL 32306, USA.
authors.forename: Likai
authors.initials: L
authors.lastname: Song
authors.affiliation: Department of Physics, Florida State University, Tallahassee, FL 32306, USA; Institute of Molecular Biophysics, Florida State University, Tallahassee, FL 32306, USA.
authors.forename: Huan-Xiang
authors.initials: HX
authors.lastname: Zhou
authors.affiliation: National High Magnetic Field Laboratory, Tallahassee, FL 32306, USA; Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL 32306, USA; Institute of Molecular Biophysics, Florida State University, Tallahassee, FL 32306, USA. Electronic address: cross@magnet.fsu.edu.
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Cross
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D004578:Electron Spin Resonance Spectroscopy; D008051:Lipid Bilayers / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009169:Mycobacterium tuberculosis / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D025941:Protein Interaction Mapping; D055503:Protein Multimerization; D012486:Salmonella typhimurium / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D008051:Lipid Bilayers
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