PDBsum entry: 3ech

Transcription, transcription regulation

PDB id: 3ech

Contents

Protein chains

129 a.a. *

135 a.a. *

24 a.a. *

Waters ×212

* Residue conservation analysis

PDB id:

3ech

Name:

Transcription, transcription regulation

Title:

The marr-family repressor mexr in complex with its antirepre

Structure:

Multidrug resistance operon repressor. Chain: a, b. Fragment: residues 1-142. Synonym: mexr. Engineered: yes. Mutation: yes. 25-mer fragment of protein armr. Chain: c. Fragment: residues 29-53.

Source:

Pseudomonas aeruginosa. Organism_taxid: 287. Gene: mexr, pa0424. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: pa3719.

Resolution:

1.80Å R-factor: 0.178 R-free: 0.229

Authors:

M.S.Wilke,N.C.J.Strynadka

Key ref:

M.S.Wilke et al. (2008). The crystal structure of MexR from Pseudomonas aeruginosa in complex with its antirepressor ArmR. Proc Natl Acad Sci U S A, 105, 14832-14837. PubMed id: 18812515 DOI: 10.1073/pnas.0805489105

Date:

30-Aug-08 Release date: 21-Oct-08

Protein chain

P52003  (MEXR_PSEAE) -  Multidrug resistance operon repressor

Seq: 147 a.a.

Struc: 129 a.a.*

Protein chain

P52003  (MEXR_PSEAE) -  Multidrug resistance operon repressor

Seq: 147 a.a.

Struc: 135 a.a.*

Protein chain

Q9HXS2  (Q9HXS2_PSEAE) -  Antirepressor for MexR, ArmR

Seq: 53 a.a.

Struc: 24 a.a.

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 

• Cellular component: intracellular (1 term)
• Biological process: transcription, DNA-dependent (2 terms)
• Biochemical function: DNA binding (2 terms)

DOI no: 10.1073/pnas.0805489105

Proc Natl Acad Sci U S A 105:14832-14837 (2008)

PubMed id: 18812515

The crystal structure of MexR from Pseudomonas aeruginosa in complex with its antirepressor ArmR.

M.S.Wilke, M.Heller, A.L.Creagh, C.A.Haynes, L.P.McIntosh, K.Poole, N.C.Strynadka.

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.

Selected figure(s)

Figure 1.
The crystal structure of the MexR[LL]–ArmR[C] complex. Cartoon of the MexR[LL] dimer (blue) in complex with ArmR[C] (orange) and cross-section of MexR[LL] (blue surface) with ArmR[C] shown in ribbon and stick representation (C, N and O atoms in orange, blue and red, respectively). Disordered segments are indicated with dashed lines.

Figure 2.
Interactions between MexR[LL] and ArmR[C]. (A) Stick representation of ArmR[C] in its binding site (MexR[LL] C atoms in blue, ArmR[C] C atoms in orange; O, N and S atoms in red, dark blue and yellow, respectively). Hydrogen bonds are shown as dashed lines and ArmR[C] labels are italicized and colored orange to distinguish them from MexR[LL] (black labels; nonprimed, chain A; primed, chain B). (B) Schematic map of interactions between MexR[LL] and residues 40–53 of ArmR[C], showing hydrogen bonds and salt bridges by dashed lines. MexR[LL] residues involved in hydrophobic contacts are listed in boxes.

Figures were selected by the author.