Abstract
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.
Highlights
To sense and to respond to environmental changes and stress conditions, all living organisms have developed different signal transduction systems
Regulation of the transcription of the genes involved in the utilization of L-malate via the malic enzyme (ME) pathway is under control of a transduction systems (TCS) of the citrate family[18], whereas the malolactic enzyme (MLE) pathway is under control of a LysR-type transcriptional regulator[19]
The search revealed that the sensor MaeK presents two transmembrane helices connected through an extracellular sensor domain consisting of a single Cache domain type 3 (PF17203), followed by a cytoplasmic PAS sensor domain (CL0183; residues 212–285), an alpha-helical domain SPOB_a (PF14689; residues 308–375) and a phospho-transferase B, C-terminal SPOB_ab domain (PF14682; residues 383–514) (Fig. 1A)
Summary
To sense and to respond to environmental changes and stress conditions, all living organisms have developed different signal transduction systems. Asp phosphorylation of the RR REC domain triggers a change in the rotameric state of highly conserved Thr/Ser and Tyr/Phe residues in β4 and β5, respectively, inducing the conformational changes observed between the active and inactive states[8, 9] This activation mechanism, named Y-T switch, seems to be predominant among RRs alternative activation modes have been described for some RR subfamilies such as NtrC9, 10. Ancillary proteins can regulate any of the three signalling reactions or work as co-sensors together with the HK, or unphosphorylated RRs can play a critical role in the regulation of gene expression[11,12,13,14,15] In this way, the combination of a highly conserved catalytic machinery with variable sensor and effector domains together with the participation of ancillary proteins, provide TCSs of an extremely high signalling plasticity allowing these systems to generate species-specific responses to similar stimulus. It has been shown that induction by low pH is independent of L-malate but requires a functional MaeK in S. pyogenes[22]
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