title: Crh, the paralogue of the phosphocarrier protein HPr, controls the methylglyoxal bypass of glycolysis in Bacillus subtilis.
abstract: The histidine protein HPr has a key role in regulation of carbohydrate utilization in low-GC Gram-positive bacteria. Bacilli possess the paralogue Crh. Like HPr, Crh becomes phosphorylated by kinase HPrK/P in response to high fructose-1,6-bisphosphate concentrations. However, Crh can only partially substitute for the regulatory functions of HPr leaving its role mysterious. Using protein co-purification, we identified enzyme methylglyoxal synthase MgsA as interaction partner of Crh in Bacillus subtilis. MgsA converts dihydroxyacetone-phosphate to methylglyoxal and thereby initiates a glycolytic bypass that prevents the deleterious accumulation of phospho-sugars under carbon overflow conditions. However, methylgyloxal is toxic and its production requires control. We show here that exclusively the non-phosphorylated form of Crh interacts with MgsA in vivo and inhibits MgsA activity in vitro. Accordingly, Crh inhibits methylglyoxal formation in vivo under nutritional famine conditions that favour a low HPr kinase activity. Thus, Crh senses the metabolic state of the cell, as reflected by its phosphorylation state, and accordingly controls flux through the harmful methylglyoxal pathway. Interestingly, HPr is unable to bind and regulate MgsA, making this a bona fide function of Crh. Four residues that differ in the interaction surfaces of HPr and Crh may account for this difference.
authors: Department of General Microbiology, Institute of Microbiology and Genetics, Georg-August-University, Grisebachstrasse 8, 37077 Göttingen, Germany.
authors: Jens J
authors: JJ
authors: Landmann
authors: Ricarda A
authors: RA
authors: Busse
authors: Jan-Hendrik
authors: JH
authors: Latz
authors: Kalpana D
authors: KD
authors: Singh
authors: Jörg
authors: J
authors: Stülke
authors: Boris
authors: B
authors: Görke
mesh_terms: D000595:Amino Acid Sequence; D001412:Bacillus subtilis / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D004099:Dihydroxyacetone Phosphate / Q000378:metabolism; D005635:Fructosediphosphates / Q000378:metabolism; D006019:Glycolysis; D053858:Metabolic Networks and Pathways; D008954:Models, Biological; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D025941:Protein Interaction Mapping; D011494:Protein Kinases / Q000378:metabolism; D011765:Pyruvaldehyde / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
chemical_list: D001426:Bacterial Proteins; C118042:Crh protein, Bacillus subtilis; D005635:Fructosediphosphates; D010750:Phosphoproteins; D004099:Dihydroxyacetone Phosphate; D011765:Pyruvaldehyde; D011494:Protein Kinases; C029063:fructose-1,6-diphosphate