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Cited by 98Bacterial Genetics and BiotechnologyProtein Structure and DynamicsEnzyme Structure and Function

Sequential binding and sensing of Zn(II) by Bacillus subtilis Zur

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Ma, Zhen, Gabriel, Scott E., Helmann, John D.·2011·Nucleic Acids Research
DOI 10.1093/nar/gkr625PMC PMC3241647
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Abstract

Bacillus subtilis Zur (BsZur) represses high-affinity zinc-uptake systems and alternative ribosomal proteins in response to zinc replete conditions. Sequence alignments and structural studies of related Fur family proteins suggest that BsZur may contain three zinc-binding sites (sites 1-3). Mutational analyses confirm the essential structural role of site 1, while mutants affected in sites 2 and 3 retain partial repressor function. Purified BsZur binds a maximum of two Zn(II) per monomer at site 1 and site 2. Site 3 residues are important for dimerization, but do not directly bind Zn(II). Analyses of metal-binding affinities reveals negative cooperativity between the two site 2 binding events in each dimer. DNA-binding studies indicate that BsZur is sequentially activated from an inactive dimer (Zur(2):Zn(2)) to a partially active asymmetric dimer (Zur(2):Zn(3)), and finally to the fully zinc-loaded active form (Zur(2):Zn(4)). BsZur with a C84S mutation in site 2 forms a Zur(2):Zn(3) form with normal metal- and DNA-binding affinities but is impaired in formation of the Zur(2):Zn(4) high affinity DNA-binding state. This mutant retains partial repressor activity in vivo, thereby supporting a model in which stepwise activation by zinc serves to broaden the physiological response to a wider range of metal concentrations.

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  • Zur proteins sense Zn2+ sufficiency and the binding of Zn2+ is anywhere from 10- to 103-fold tighter when measured in the presence of DNA.

    “For example, Zur proteins sense Zn2+ sufficiency and the binding of Zn2+ is anywhere from 10- to 103-fold tighter when measured in the presence of DNA.25,27,28”

    From Metals in Motion: Understanding Labile Metal Pools in Bacteria (2025) · cites this paper as [25]

  • For some regulatory proteins there are multiple metal-binding sites in the functional oligomer and these may bind with negative cooperativity.

    “For some regulatory proteins there are multiple metal-binding sites in the functional oligomer and these may bind with negative cooperativity.25”

    From Metals in Motion: Understanding Labile Metal Pools in Bacteria (2025) · cites this paper as [25]

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Research works printed but not linked: 25

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Authors
Ma, Z., Gabriel, S. E., & Helmann, J. D.
Affiliations
Cornell University (US)
Corresponding author
Helmann, John D.
ORCID
Venue
Nucleic Acids Research
Publisher
Oxford University Press (OUP)
Published
2011-08-05
Volume
39
Issue
21
Pages
9130-9138
ISSN
  • 0305-1048 (ISSN-L)
  • 1362-4962
DOI
10.1093/nar/gkr625
PMC
PMC3241647
OpenAlex
W2051328663
Cited by
98
References
7
Citations by year
2026: 2 · 2025: 3 · 2024: 5 · 2023: 2 · 2022: 5 · 2021: 5 · 2020: 8 · 2019: 13 · 2018: 4 · 2017: 11 · 2016: 6 · 2015: 5 · 2014: 13 · 2013: 7 · 2012: 5
FWCI
5.03
Type
journal article
Language
en
Open access
Licence
Locations
  • Nucleic Acids Research (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Institute of General Medical Sciences (GM059323, R01GM059323)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
Keywords
zinc binding site, dimerization, DNA binding, metal sensing, negative cooperativity
MeSH terms
Bacillus subtilis, Bacterial Proteins, Binding Sites, DNA, Mutation, Protein Binding, Repressor Proteins, Zinc, Dimerization

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