3MWM

Graded expression of zinc-responsive genes through two regulatory zinc-binding sites in Zur

Summary for 3MWM

• Entry DOI: 10.2210/pdb3mwm/pdb
• Descriptor: Putative metal uptake regulation protein, ZINC ION (3 entities in total)
• Functional Keywords: fur, zur, regulatory metal, graded transcription regulation, transcription
• Biological source: Streptomyces coelicolor
• Total number of polymer chains: 2
• Total formula weight: 29795.27

Authors

Jung, H.J.,An, Y.J.,Cha, S.-S. (deposition date: 2010-05-06, release date: 2011-03-16, Last modification date: 2023-11-01)

Primary citation

Shin, J.-H.,Jung, H.J.,An, Y.J.,Cho, Y.-B.,Cha, S.-S.,Roe, J.-H.
Graded expression of zinc-responsive genes through two regulatory zinc-binding sites in Zur
Proc.Natl.Acad.Sci.USA, 108:5045-5050, 2011

PubMed Abstract: Zinc is one of the essential transition metals in cells. Excess or lack of zinc is detrimental, and cells exploit highly sensitive zinc-binding regulators to achieve homeostasis. In this article, we present a crystal structure of active Zur from Streptomyces coelicolor with three zinc-binding sites (C-, M-, and D-sites). Mutations of the three sites differentially affected sporulation and transcription of target genes, such that C- and M-site mutations inhibited sporulation and derepressed all target genes examined, whereas D-site mutations did not affect sporulation and derepressed only a sensitive gene. Biochemical and spectroscopic analyses of representative metal site mutants revealed that the C-site serves a structural role, whereas the M- and D-sites regulate DNA-binding activity as an on-off switch and a fine-tuner, respectively. Consistent with differential effect of mutations on target genes, zinc chelation by TPEN derepressed some genes (znuA, rpmF2) more sensitively than others (rpmG2, SCO7682) in vivo. Similar pattern of TPEN-sensitivity was observed for Zur-DNA complexes formed on different promoters in vitro. The sensitive promoters bound Zur with lower affinity than the less sensitive ones. EDTA-treated apo-Zur gained its DNA binding activity at different concentrations of added zinc for the two promoter groups, corresponding to free zinc concentrations of 4.5×10(-16) M and 7.9×10(-16) M for the less sensitive and sensitive promoters, respectively. The graded expression of target genes is a clever outcome of subtly modulating Zur-DNA binding affinities in response to zinc availability. It enables bacteria to detect metal depletion with improved sensitivity and optimize gene-expression pattern.

PubMed: 21383173
DOI: 10.1073/pnas.1017744108

Experimental method

X-RAY DIFFRACTION (2.4 Å)