3ECH

The MarR-family repressor MexR in complex with its antirepressor ArmR

Summary for 3ECH

• Entry DOI: 10.2210/pdb3ech/pdb
• Descriptor: Multidrug resistance operon repressor, 25-mer fragment of protein ArmR (3 entities in total)
• Functional Keywords: winged helix, helix-turn-helix, protein-peptide complex, dna-binding, repressor, transcription, transcription regulation
• Biological source: Pseudomonas aeruginosa; More
• Total number of polymer chains: 3
• Total formula weight: 36144.62

Authors

Wilke, M.S.,Strynadka, N.C.J. (deposition date: 2008-08-30, release date: 2008-10-21, Last modification date: 2023-08-30)

Primary citation

Wilke, M.S.,Heller, M.,Creagh, A.L.,Haynes, C.A.,McIntosh, L.P.,Poole, K.,Strynadka, N.C.J.
The crystal structure of MexR from Pseudomonas aeruginosa in complex with its antirepressor ArmR
Proc.Natl.Acad.Sci.Usa, 105:14832-14837, 2008

PubMed Abstract: The intrinsic antimicrobial resistance of the opportunistic human pathogen Pseudomonas aeruginosa is compounded in mutant strains that overexpress multidrug efflux pumps such as the prominent drug-proton antiporter, MexAB-OprM. The primary regulator of the mexAB-oprM operon is the MarR family repressor, MexR. An additional repressor, NalC, also regulates mexAB-oprM by controlling expression of ArmR, an antirepressor peptide that is hypothesized to prevent the binding of MexR to its cognate DNA operator via an allosteric protein-peptide interaction. To better understand how ArmR modulates MexR, we determined the MexR-binding region of ArmR as its C-terminal 25 residues and solved the crystal structure of MexR in a 2:1 complex with this ArmR fragment at 1.8 A resolution. This structure reveals that the C-terminal residues of ArmR form a kinked alpha-helix, which occupies a pseudosymmetrical and largely hydrophobic binding cavity located at the centre of the MexR dimer. Although the ArmR-binding cavity partially overlaps with the small molecule effector-binding sites of other MarR family members, it possesses a larger and more complex binding surface to accommodate the greater size and specific physicochemical properties of a peptide effector. Comparison with the structure of apo-MexR reveals that ArmR stabilizes a dramatic conformational change that is incompatible with DNA-binding. Thus, this work defines the structural mechanism by which ArmR allosterically derepresses MexR-controlled gene expression in P. aeruginosa and reveals important insights into the regulation of multidrug resistance.

PubMed: 18812515
DOI: 10.1073/pnas.0805489105

Experimental method

X-RAY DIFFRACTION (1.802 Å)