Database accession: MF7000618
Name: MexR R21W derepressor mutant (Pseudomonas aeruginosa)
PDB ID: 4zzl
Experimental method: X-ray (2.19 Å)
Assembly: Homodimer
Source organism: Pseudomonas aeruginosa
Primary publication of the structure:
Anandapadamanaban M, Pilstål R, Andresen C, Trewhella J, Moche M, Wallner B, Sunnerhagen M
Mutation-Induced Population Shift in the MexR Conformational Ensemble Disengages DNA Binding: A Novel Mechanism for MarR Family Derepression.
(2016) Structure 24: 1311-1321
PMID: 27427478
Abstract:
MexR is a repressor of the MexAB-OprM multidrug efflux pump operon of Pseudomonas aeruginosa, where DNA-binding impairing mutations lead to multidrug resistance (MDR). Surprisingly, the crystal structure of an MDR-conferring MexR mutant R21W (2.19 Å) presented here is closely similar to wild-type MexR. However, our extended analysis, by molecular dynamics and small-angle X-ray scattering, reveals that the mutation stabilizes a ground state that is deficient of DNA binding and is shared by both mutant and wild-type MexR, whereas the DNA-binding state is only transiently reached by the more flexible wild-type MexR. This population shift in the conformational ensemble is effected by mutation-induced allosteric coupling of contact networks that are independent in the wild-type protein. We propose that the MexR-R21W mutant mimics derepression by small-molecule binding to MarR proteins, and that the described allosteric model based on population shifts may also apply to other MarR family members.
Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown. Molecular function:
DNA-binding transcription repressor activity DNA-binding transcription repressor activity
identical protein binding identical protein binding
transcription cis-regulatory region binding transcription cis-regulatory region binding
Biological process:
negative regulation of DNA-templated transcription negative regulation of DNA-templated transcription
negative regulation of protein secretion negative regulation of protein secretion
negative regulation of transmembrane transport negative regulation of transmembrane transport
Cellular component:
protein-DNA complex protein-DNA complex
Structural annotations of the participating protein chains.Entry contents: 2 distinct polypeptide molecules
Chains: A, B
Notes: All chains according to the most probable oligomerization state stored in PDBe were considered.
Number of unique protein segments: 1
Name: Multidrug resistance operon repressor
Source organism: Pseudomonas aeruginosa
Length: 147 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMNYPVNPDLMPALMAVFQHVRTRIQSELDCQRLDLTPPDVHVLKLIDEQRGLNLQDLGRQMCRDKALITRKIRELEGRNLVRRERNPSDQRSFQLFLTDEGLAIHQHAEAIMSRVHDELFAPLTPVEQATLVHLLDQCLAAQPLEDI
UniProtKB AC: P52003 (positions: 5-139)
Coverage: 91%
Name: Multidrug resistance operon repressor
Source organism: Pseudomonas aeruginosa
Length: 147 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMNYPVNPDLMPALMAVFQHVRTRIQSELDCQRLDLTPPDVHVLKLIDEQRGLNLQDLGRQMCRDKALITRKIRELEGRNLVRRERNPSDQRSFQLFLTDEGLAIHQHAEAIMSRVHDELFAPLTPVEQATLVHLLDQCLAAQPLEDI
UniProtKB AC: P52003 (positions: 5-139)
Coverage: 91%
Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding. Representative domain in related structures: Winged helix DNA-binding domain (MarR type I) transcriptional regulator
Evidence level: Direct evidence
Evidence coverage: Only some parts of the structure participates in mutual synergistic folding.
Complex Evidence:
The MarR-type family transcriptional regulator, NadR is dimeric in solution (SE-HPLC/MALLS) as other MarR faimily proteins (PMID:18272181). Compared to ligand-stabilized holo-NadR, apo-NadR displayed an intrinsic flexibility focused in the DNA-binding region (PMID:27105075). The structural features of several family members have been described, they all have two subdomains: there is a helix-turn-helix (HTH) DNA-binding domain plus dimerization helices that form an interlocked dimerization domain. Dimerization is mediated by helices α1, α5, and α6 from each monomer resulting in an interlocked, tight dimer burying a large, hydrophobic solvent-accessible surface area. The structure of the dimerization region reveals domain swapping, where α1 of one subunit is inserted between α5′ and α6′ of the other subunit and forms a coiled coil with helix α6′ (PMID:19586910). The DNA-binding elements contain helices α3-α4 and strands β1-β2 from each monomer (PMID:29794028, PMID:35367827).
Chain A:
N/A
Chain B:
N/A
Surface and contacts features:
Structures from the PDB that contain the same number of proteins, and the proteins from the two structures show a sufficient degree of pairwise similarity, i.e. they belong to the same UniRef90 cluster (the full proteins exhibit at least 90% sequence identity) and convey roughly the same region to their respective interactions (the two regions from the two proteins share a minimum of 70% overlap). Download the CIF file (.cif)
Download this entry's XML file (.xml)
Download this entry's JSON file (.json)
