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Crystal Structure of the Zinc-Dependent MarR Family Transcriptional Regulator AdcR in the Zn(II)-Bound State

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journal contribution
posted on 14.12.2011, 00:00 authored by Alfredo J. Guerra, Charles E. Dann, David P. Giedroc
Streptococcus pneumoniae adhesin competence regulator (AdcR), the first metal-dependent member of the multiple antibiotic resistance regulator (MarR) family of proteins, represses the transcription of a high-affinity zinc-specific uptake transporter, a group of surface antigen zinc-binding pneumococcal histidine triad proteins (PhtA, PhtB, PhtD, and PhtE), and an AdcA homologue (AdcAII). The 2.0 Å resolution structure of Zn(II)-bound AdcR reveals a highly helical two-fold-symmetric dimer with two distinct metal-binding sites per protomer. Zn(II) is tetrahedrally coordinated by E24, H42, H108, and H112 in what defines the primary sensing site in AdcR. Site 2 is a tetracoordinate site whose function is currently unknown. NMR methyl group perturbation experiments reveal that Zn(II) drives a global change in the structure of apo-AdcR that stabilizes a conformation that is compatible with DNA binding. This co-repression mechanism is unprecedented in MarR transcriptional regulators.

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