Crystal structure of the VanR transcription factor and the role of its unique alpha-helix in effector recognition.
Kwak, Y.M., Park, S.C., Na, H.W., Kang, S.G., Lee, G.S., Ko, H.J., Kim, P.H., Oh, B.C., Yoon, S.I.(2018) FEBS J 285: 3786-3800
- PubMed: 30095229 
- DOI: https://doi.org/10.1111/febs.14629
- Primary Citation of Related Structures:  
5Z7B - PubMed Abstract: 
VanR is a negative transcriptional regulator of bacteria that belongs to the PadR family and modulates the expression of vanillate transport and degradation proteins in response to vanillate. Although VanR plays a key role in the utilization of vanillate as a carbon source, it is barely understood how VanR recognizes its effector. Thus, our knowledge concerning the gene regulatory mechanism of VanR is limited. Here, we reveal the vanillate-binding mode of VanR through structural, biophysical, and mutational studies. Similar to other PadR family members, VanR forms a functional dimer, and each VanR subunit consists of an N-terminal DNA-binding domain (NTD) and a C-terminal dimerization domain (CTD). One VanR dimer simultaneously binds two vanillate molecules using two interdomain cavities, as observed in PadR. In contrast to these common features, VanR contains an additional ¦Á-helix, ¦Ái, that has not been found in other PadR family members. The ¦Ái helix functions as an interdomain crosslinker that mediates interactions between the NTD and the CTD. In addition, the VanR-specific ¦Ái helix plays a key role in the formation of a unique effector-binding site. As a result, the effector-binding mode of VanR is distinguishable from that of PadR in the location and accessibility of the effector-binding site as well as the orientation of its bound effector. Furthermore, we propose the DNA-binding mode and vanillate-mediated transcriptional regulation mechanism of VanR based on comparative structural and mutational analyses. DATABASES: The atomic coordinates and the structure factors for VanR (PDB ID 5Z7B) have been deposited in the Protein Data Bank, www.pdb.org.
Organizational Affiliation: 
Division of Biomedical Convergence, College of Biomedical Science, Kangwon National University, Chuncheon, Korea.