The malate sensing two-component system MaeKR is a non-canonical class of sensory complex for C4-dicarboxylates

• Published in: Scientific reports Vol. 7; no. 1; pp. 2708 - 16
• Main Authors: Miguel-Romero, L., Casino, P., Landete, J. M., Monedero, V., Zúñiga, M., Marina, A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02.06.2017; Nature Publishing Group; Nature Portfolio
• Subjects: 38; 631/326/88; 631/535/1266; 82; 96; Adenosine Triphosphate - chemistry; Adenosine Triphosphate - metabolism; Amino Acid Sequence; Bacterial Proteins - chemistry; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Citric acid; Colonization; Conformation; Conserved Sequence; Dicarboxylic Acids - metabolism; Dimerization; Genotype & phenotype; Histidine; Histidine kinase; Humanities and Social Sciences; Kinases; Lactobacillus casei - classification; Lactobacillus casei - physiology; Malates - metabolism; Malic enzyme; Models, Biological; Models, Molecular; Monomers; multidisciplinary; Phosphorylation; Phylogeny; Promoter Regions, Genetic; Protein Binding; Protein Conformation; Protein Interaction Domains and Motifs; Protein Multimerization; Science; Science (multidisciplinary); Signal transduction; Transduction
• DOI: 10.1038/s41598-017-02900-z
• ISSN: 2045-2322

Microbial colonization of different environments is enabled to a great extent by the plasticity of their sensory mechanisms, among them, the two-component signal transduction systems (TCS). Here, an example of TCS plasticity is presented: the regulation of L-malate catabolism via malic enzyme by MaeRK in Lactobacillales . MaeKR belongs to the citrate family of TCS as the Escherichia coli DcuSR system. We show that the Lactobacillus casei histidine-kinase MaeK is defective in autophosphorylation activity as it lacks a functional catalytic and ATP binding domain. The cognate response regulator MaeR was poorly phosphorylated at its phosphoacceptor Asp in vitro . This phosphorylation, however, enhanced MaeR binding in vitro to its target sites and it was required for induction of regulated genes in vivo . Elucidation of the MaeR structure revealed that response regulator dimerization is accomplished by the swapping of α4-β5-α5 elements between two monomers, generating a phosphoacceptor competent conformation. Sequence and phylogenetic analyses showed that the MaeKR peculiarities are not exclusive to L. casei as they are shared by the rest of orthologous systems of Lactobacillales . Our results reveal MaeKR as a non-canonical TCS displaying distinctive features: a swapped response regulator and a sensor histidine kinase lacking ATP-dependent kinase activity.