Binding of MgtR, a Salmonella Transmembrane Regulatory Peptide, to MgtC, a Mycobacterium tuberculosis Virulence Factor: A Structural Study
详细信息 查看全文
- 作者：Frantz L. Jean-Francois ; Jian Dai ; Lu Yu ; Alissa Myrick ; Eric Rubin ; Piotr G. Fajer ; Likai Song ; Huan-Xiang Zhou ; Timothy A. Cross
- 关键词：PISEMA ; polarization inversion spin exchange at the magic angle ; MD ; molecular dynamics
- 刊名：Journal of Molecular Biology
- 出版年：23 January, 2014
- 年：2014
- 卷：426
- 期：2
- 页码：436-446
- 全文大小：923 K
文摘
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.