Structural insight into glucose repression of the mannitol operon

• Published in: Scientific reports 2019-09, Vol.9 (1), p.13930-11, Article 13930
• Main Authors: Choe, Mangyu, Min, Huitae, Park, Young-Ha, Kim, Yeon-Ran, Woo, Jae-Sung, Seok, Yeong-Jae
• Format: Article
• Language: English
• Subjects: 38; 631/326/1320; 631/535/1266; 82; Bacterial Proteins - chemistry; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Carbohydrates; Catabolite repression; Crystallography, X-Ray; E coli; Enzyme I; Escherichia coli; Escherichia coli Proteins - chemistry; Escherichia coli Proteins - genetics; Escherichia coli Proteins - metabolism; Gene silencing; Glucose - metabolism; Glucose transport; Humanities and Social Sciences; Kinases; Mannitol; Mannitol - metabolism; Metabolism; Molecular Dynamics Simulation; multidisciplinary; Mutation; Operon; Phosphoenolpyruvate Sugar Phosphotransferase System - chemistry; Phosphoenolpyruvate Sugar Phosphotransferase System - genetics; Phosphoenolpyruvate Sugar Phosphotransferase System - metabolism; Phosphorylation; Phosphotransferase; Protein Binding; Repressor Proteins - chemistry; Repressor Proteins - genetics; Repressor Proteins - metabolism; Science; Science (multidisciplinary)
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-50249-2

Carbon catabolite repression is a regulatory mechanism to ensure sequential utilization of carbohydrates and is usually accomplished by repression of genes for the transport and metabolism of less preferred carbon compounds by a more preferred one. Although glucose and mannitol share the general components, enzyme I and HPr, of the phosphoenolpyruvate-dependent phosphotransferase system (PTS) for their transport, glucose represses the transport and metabolism of mannitol in a manner dependent on the mannitol operon repressor MtlR in Escherichia coli . In a recent study, we identified the dephosphorylated form of HPr as a regulator determining the glucose preference over mannitol by interacting with and augmenting the repressor activity of MtlR in E. coli . Here, we determined the X-ray structure of the MtlR-HPr complex at 3.5 Å resolution to understand how phosphorylation of HPr impedes its interaction with MtlR. The phosphorylation site (His15) of HPr is located close to Glu108 and Glu140 of MtlR and phosphorylation at His15 causes electrostatic repulsion between the two proteins. Based on this structural insight and comparative sequence analyses, we suggest that the determination of the glucose preference over mannitol solely by the MtlR-HPr interaction is conserved within  the Enterobacteriaceae family.