Document Type
Article
Publication Date
2012
Publication Title
PNAS
Volume
110
Issue
44
Pages
17820-17825
Publisher Name
National Academy of Sciences of the United States of America
Abstract
Bacillus subtilis GabR is a transcription factor that regulates gamma-aminobutyric acid (GABA) metabolism. GabR is a member of the understudied MocR/GabR subfamily of the GntR family of transcription regulators. A typical MocR/GabR-type regulator is a chimeric protein containing a short N-terminal helix-turn-helix DNA-binding domain and a long C-terminal pyridoxal 5′-phosphate (PLP)-binding putative aminotransferase domain. In the presence of PLP and GABA, GabR activates the gabTD operon, which allows the bacterium to use GABA as nitrogen and carbon sources. GabR binds to its own promoter and represses gabRtranscription in the absence of GABA. Here, we report two crystal structures of full-length GabR from B. subtilis: a 2.7-Å structure of GabR with PLP bound and the 2.55-Å apo structure of GabR without PLP. The quaternary structure of GabR is a head-to-tail domain-swap homodimer. Each monomer comprises two domains: an N-terminal winged-helix DNA-binding domain and a C-terminal PLP-binding type I aminotransferase-like domain. The winged-helix domain contains putative DNA-binding residues conserved in other GntR-type regulators. Together with sedimentation velocity and fluorescence polarization assays, the crystal structure of GabR provides insights into DNA binding by GabR at the gabR and gabT promoters. The absence of GabR-mediated aminotransferase activity in the presence of GABA and PLP, and the presence of an active site configuration that is incompatible with stabilization of the GABA external aldimine suggest that a GabR aminotransferase-like activity involving GABA and PLP is not essential to its primary function as a transcription regulator.
Recommended Citation
Raji Edayathumangalam, Rui Wu, Roman Garcia, Yuguang Wang, Wei Wang, Cheryl A. Kreinbring, Alicia Bach, Jingling Liao, Todd A. Stone, Thomas C. Terwilliger, Quyen Q. Hoang, Boris R. Belitsky, Gregory A. Petsko, Dagmar Ringe, and Dali Liu. "Crystal Structure of Bacillus Subtilis GabR, an Autorepressor and Transcriptional Activator of gabT." PNAS 110(44), 2013.
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Copyright Statement
© National Academy of Sciences of the United States of America, 2013.
Comments
Author Posting. © National Academy of Sciences of the United States of America, 2013. This article is posted here by permission of the National Academy of Sciences of the United States of America for personal use, not for redistribution. The article was published in PNAS, Volume 110, Issue 44, October 2013, http://dx.doi.org/10.1073/pnas.1315887110