Domain architecture of the Mycobacterium tuberculosis MabR (Rv2242), a member of the PucR transcription factor family
Véronique Megalizzi,
Abdalkarim Tanina,
Camille Grosse,
Manon Mirgaux,
Pierre Legrand,
Gaëtan Dias Mirandela,
Alexandre Wohlkönig,
Pablo Bifani,
René Wintjens
Affiliations
Véronique Megalizzi
Unit of Microbiology, Bioorganic and Macromolecular Chemistry, Department of Research in Drug Development, Faculty of Pharmacy, Université Libre de Bruxelles, Belgium
Abdalkarim Tanina
Unit of Microbiology, Bioorganic and Macromolecular Chemistry, Department of Research in Drug Development, Faculty of Pharmacy, Université Libre de Bruxelles, Belgium
Camille Grosse
Unit of Microbiology, Bioorganic and Macromolecular Chemistry, Department of Research in Drug Development, Faculty of Pharmacy, Université Libre de Bruxelles, Belgium
Manon Mirgaux
Unit of Microbiology, Bioorganic and Macromolecular Chemistry, Department of Research in Drug Development, Faculty of Pharmacy, Université Libre de Bruxelles, Belgium; Laboratoire de Chimie Biologique Structurale (CBS), Unité de Chimie Physique Théorique et Structurale (UCPTS), Department of Chemistry, Faculty of Sciences, University of Namur, Belgium; Center of Microscopy and Molecular Imaging (CMMI), Biopark Charleroi, Université Libre de Bruxelles, Gosselies, Belgium
Pierre Legrand
SOLEIL synchrotron, Gif-sur-Yvette, France
Gaëtan Dias Mirandela
Biology of Membrane Transport Laboratory, Molecular Biology Department, Faculty of Sciences, Université Libre de Bruxelles, Belgium
Alexandre Wohlkönig
Center for Structural Biology, Vlaams Institute voor Biotechnology (VIB), Brussels, Belgium
Pablo Bifani
A∗STAR Infectious Diseases Laboratory, Agency for Science, Technology and Research (A∗STAR), Singapore; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
René Wintjens
Unit of Microbiology, Bioorganic and Macromolecular Chemistry, Department of Research in Drug Development, Faculty of Pharmacy, Université Libre de Bruxelles, Belgium; Corresponding author.
MabR (Rv2242), a PucR-type transcription factor, plays a crucial role in regulating mycolic acid biosynthesis in Mycobacterium tuberculosis. To understand its regulatory mechanisms, we determined the crystal structures of its N-terminal and C-terminal domains. The N-terminal domain adopts a globin-like fold, while the C-terminal domain comprises an α/β GGDEF domain and an all-α effector domain with a helix-turn-helix DNA-binding motif. This unique domain combination is specific to Actinomycetes. Biochemical and computational studies suggest that full-length MabR forms both dimeric and tetrameric assemblies in solution. Structural analysis revealed two distinct dimerization interfaces within the N- and C-terminal domains, further supporting a tetrameric organization. These findings provide valuable insights into the domain architecture, oligomeric state, and potential regulatory mechanisms of MabR.
