The quorum-sensing (QS) system between the phages and their hosts is important for the phage lysis-lysogeny decision. In Vibrio cholerae, the QS system consists of a LuxR-type receptor VqmA (VqmAVc) and an autoinducer molecule 3,5-dimethylpyrazin-2-ol (DPO). A VqmA homolog encoded by vibriophage VP882 (VqmAPhage) can intervene the host QS system via binding to both the host-produced DPO and its cognate promoter (Pqtip) to induce the phage lysogeny-to-lysis transition, whereas VqmAVc cannot influence the VqmAPhage-induced pathway, suggesting an asymmetry regulation. In this study, we report the crystal structure of VqmAPhage-DPO complex at 2.65 Å and reveal that the mechanism of DPO recognition is conserved in VqmA homologs. Besides, we identify a non-classical palindrome sequence in Pqtip, which can be effectively recognized by VqmAPhage but not VqmAVc. The sequence contains an interval longer than that in the vqmR promoter recognized by VqmAVc. In addition, the two DBD regions in the VqmAPhage dimer exhibit more relaxed architecture than that of the reported VqmAVc, which is likely to be in the conformation that may easily bind to target promoter containing a longer interval. In summary, our findings provide a structural and biochemical basis for the DBD-dependent DNA recognition in different promoter regions in the phage lysogeny-to-lysis decision communication system, and provide clues for developing phage therapies against Vibrio cholerae infection.
Keywords: Asymmetric gene regulation; Crystal structure; DNA recognition; Lysis-lysogeny decision; VqmA(Phage)-DPO.
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