5X5L

Crystal structure of response regulator AdeR DNA binding domain in complex with an intercistronic region

Summary for 5X5L

• Entry DOI: 10.2210/pdb5x5l/pdb
• Related: 5X5J
• Descriptor: AdeR, DNA (5'-D(P*TP*AP*AP*AP*GP*TP*GP*TP*GP*GP*AP*GP*TP*AP*AP*GP*TP*GP*TP*GP*GP*AP*GP*A)-3'), DNA (5'-D(P*TP*CP*TP*CP*CP*AP*CP*AP*CP*TP*TP*AP*CP*TP*CP*CP*AP*CP*AP*CP*TP*TP*TP*A)-3'), ... (4 entities in total)
• Functional Keywords: bacterial signaling transduction, two-component regulatory system, response regulator, ader, dna binding protein-dna complex, dna binding protein/dna
• Biological source: Acinetobacter baumannii; More
• Total number of polymer chains: 10
• Total formula weight: 106967.64

Authors

Wen, Y. (deposition date: 2017-02-16, release date: 2017-08-30, Last modification date: 2023-11-22)

Primary citation

Wen, Y.,Ouyang, Z.,Yu, Y.,Zhou, X.,Pei, Y.,Devreese, B.,Higgins, P.G.,Zheng, F.
Mechanistic insight into how multidrug resistant Acinetobacter baumannii response regulator AdeR recognizes an intercistronic region.
Nucleic Acids Res., 45:9773-9787, 2017

PubMed Abstract: AdeR-AdeS is a two-component regulatory system, which controls expression of the adeABC efflux pump involved in Acinetobacter baumannii multidrug resistance. AdeR is a response regulator consisting of an N-terminal receiver domain and a C-terminal DNA-binding-domain. AdeR binds to a direct-repeat DNA in the intercistronic region between adeR and adeABC. We demonstrate a markedly high affinity binding between unphosphorylated AdeR and DNA with a dissociation constant of 20 nM. In addition, we provide a 2.75 Å crystal structure of AdeR DNA-binding-domain complexed with the intercistronic DNA. This structure shows that the α3 and β hairpin formed by β5-β6 interacts with the major and minor groove of the DNA, which in turn leads to the introduction of a bend. The AdeR receiver domain structure revealed a dimerization motif mediated by a gearwheel-like structure involving the D108F109-R122 motif through cation π stack interaction. The structure of AdeR receiver domain bound with magnesium indicated a conserved Glu19Asp20-Asp63 magnesium-binding motif, and revealed that the potential phosphorylation site Asp63OD1 forms a hydrogen bond with Lys112. We thus dissected the mechanism of how AdeR recognizes the intercistronic DNA, which leads to a diverse mode of response regulation. Unlocking the AdeRS mechanism provides ways to circumvent A. baumannii antibiotic resistance.

PubMed: 28934482
DOI: 10.1093/nar/gkx624

Experimental method

X-RAY DIFFRACTION (2.75 Å)