Structural and Biochemical Characterization of the Francisella tularensis Pathogenicity Regulator, Macrophage Locus Protein A (MglA)

摘要: Francisella tularensis is one of the most infectious bacteria known and etiologic agent tularemia. virulence arises from a 33 kilobase (Kb) pathogenicity island (FPI) that regulated by macrophage locus protein A (MglA) stringent starvation (SspA). These proteins interact with both RNA polymerase (RNAP) gene regulator (PigR) to activate FPI transcription. However, molecular mechanisms involved are not well understood. Indeed, while bacterial SspA function as homodimers transcription, F. forms heterodimer MglA protein, which unique tularensis. To gain insight into function, we performed structural biochemical studies. The structure revealed it contains fold similar family. Unexpectedly, also formed homodimer in crystal. Chemical crosslinking size exclusion chromatography (SEC) studies showed able self-associate solution form dimer but preferentially heterodimerizes SspA. Finally, malate, was used crystallization, bound an open pocket dimer, suggesting possibility this cleft could small molecule ligand binding. location binding region relative recently mapped PigR RNAP interacting sites suggest possible roles for SspA•MglA function.