2KSS

NMR structure of Myxococcus xanthus antirepressor CarS1

Summary for 2KSS

• Entry DOI: 10.2210/pdb2kss/pdb
• Descriptor: Carotenogenesis protein carS (1 entity in total)
• Functional Keywords: protein, antirepressor, activator, carotenoid biosynthesis, transcription, transcription regulation, transcription regulator
• Biological source: Myxococcus xanthus
• Total number of polymer chains: 1
• Total formula weight: 11488.88

Authors

Jimenez, M.,Gonzalez, C.,Padmanabhan, S.,Leon, E.,Navarro-Aviles, G.,Elias-Arnanz, M. (deposition date: 2010-01-13, release date: 2010-05-12, Last modification date: 2024-05-01)

Primary citation

Leon, E.,Navarro-Aviles, G.,Santiveri, C.M.,Flores-Flores, C.,Rico, M.,Gonzalez, C.,Murillo, F.J.,Elias-Arnanz, M.,Jimenez, M.A.,Padmanabhan, S.
A bacterial antirepressor with SH3 domain topology mimics operator DNA in sequestering the repressor DNA recognition helix.
Nucleic Acids Res., 38:5226-5241, 2010

PubMed Abstract: Direct targeting of critical DNA-binding elements of a repressor by its cognate antirepressor is an effective means to sequester the repressor and remove a transcription initiation block. Structural descriptions for this, though often proposed for bacterial and phage repressor-antirepressor systems, are unavailable. Here, we describe the structural and functional basis of how the Myxococcus xanthus CarS antirepressor recognizes and neutralizes its cognate repressors to turn on a photo-inducible promoter. CarA and CarH repress the carB operon in the dark. CarS, produced in the light, physically interacts with the MerR-type winged-helix DNA-binding domain of these repressors leading to activation of carB. The NMR structure of CarS1, a functional CarS variant, reveals a five-stranded, antiparallel beta-sheet fold resembling SH3 domains, protein-protein interaction modules prevalent in eukaryotes but rare in prokaryotes. NMR studies and analysis of site-directed mutants in vivo and in vitro unveil a solvent-exposed hydrophobic pocket lined by acidic residues in CarS, where the CarA DNA recognition helix docks with high affinity in an atypical ligand-recognition mode for SH3 domains. Our findings uncover an unprecedented use of the SH3 domain-like fold for protein-protein recognition whereby an antirepressor mimics operator DNA in sequestering the repressor DNA recognition helix to activate transcription.

PubMed: 20410074
DOI: 10.1093/nar/gkq277

Experimental method

SOLUTION NMR