5HLI

Structure of Disulfide formed AbfR

Summary for 5HLI

• Entry DOI: 10.2210/pdb5hli/pdb
• Related: 5HLG 5HLH
• Descriptor: MarR family transcriptional regulator, COPPER (II) ION, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: disulfide, transcription factor, transcription regulator, transcription regulator
• Biological source: Staphylococcus epidermidis
• Total number of polymer chains: 2
• Total formula weight: 35498.34

Authors

Liu, G.,Liu, X.,Gan, J.,Yang, C.-G. (deposition date: 2016-01-15, release date: 2017-01-25, Last modification date: 2024-10-23)

Primary citation

Liu, G.,Liu, X.,Xu, H.,Liu, X.,Zhou, H.,Huang, Z.,Gan, J.,Chen, H.,Lan, L.,Yang, C.G.
Structural Insights into the Redox-Sensing Mechanism of MarR-Type Regulator AbfR.
J. Am. Chem. Soc., 139:1598-1608, 2017

PubMed Abstract: As a master redox-sensing MarR-family transcriptional regulator, AbfR participates in oxidative stress responses and virulence regulations in Staphylococcus epidermidis. Here, we present structural insights into the DNA-binding mechanism of AbfR in different oxidation states by determining the X-ray crystal structures of a reduced-AbfR/DNA complex, an overoxidized (Cys13-SOH and Cys13-SOH) AbfR/DNA, and 2-disulfide cross-linked AbfR dimer. Together with biochemical analyses, our results suggest that the redox regulation of AbfR-sensing displays two novel features: (i) the reversible disulfide modification, but not the irreversible overoxidation, significantly abolishes the DNA-binding ability of the AbfR repressor; (ii) either 1-disulfide cross-linked or 2-disulfide cross-linked AbfR dimer is biologically significant. The overoxidized species of AbfR, resembling the reduced AbfR in conformation and retaining the DNA-binding ability, does not exist in biologically significant concentrations, however. The 1-disulfide cross-linked modification endows AbfR with significantly weakened capability for DNA-binding. The 2-disulfide cross-linked AbfR adopts a very "open" conformation that is incompatible with DNA-binding. Overall, the concise oxidation chemistry of the redox-active cysteine allows AbfR to sense and respond to oxidative stress correctly and efficiently.

PubMed: 28086264
DOI: 10.1021/jacs.6b11438

Experimental method

X-RAY DIFFRACTION (2.05 Å)