A metallothionein containing a zinc finger within a four-metal cluster protects a bacterium from zinc toxicity

J.A. Parkinson, C.A. Blindauer, M.D. Harrison, A.K. Robinson, J.S. Turner-Cavfet, N.J. Robinson, P.J. Sadler

Research output: Contribution to journalConference Contribution

132 Citations (Scopus)

Abstract

Zinc is essential for many cellular processes, including DNA synthesis, transcription, and translation, but excess can be toxic. A zinc-induced gene, smtA, is required for normal zinc-tolerance in the cyanobacterium Synechococcus PCC 7942. Here we report that the protein SmtA contains a cleft lined with Cys-sulfur and His-imidazole ligands that binds four zinc ions in a Zn4Cys9His2 cluster. The thiolate sulfurs of five Cys ligands provide bridges between the two ZnCys4 and two ZnCys3His sites, giving two fused six-membered rings with distorted boat conformations. The inorganic core strongly resembles the Zn4Cys11 cluster of mammalian metallothionein, despite different amino acid sequences, a different linear order of the ligands, and presence of histidine ligands. Also, SmtA contains elements of secondary structure not found in metallothioneins. One of the two Cys4-coordinated zinc ions in SmtA readily exchanges with exogenous metal (111Cd), whereas the other is inert. The thiolate sulfur ligands bound to zinc in this site are buried within the protein. Regions of β-strand and α-helix surround the inert site to form a zinc finger resembling the zinc fingers in GATA and LIM-domain proteins. Eukaryotic zinc fingers interact specifically with other proteins or DNA and an analogous interaction can therefore be anticipated for prokaryotic zinc fingers. SmtA now provides structural proof for the existence of zinc fingers in prokaryotes, and sequences related to the zinc finger motif can be identified in several bacterial genomes.
LanguageEnglish
Pages9593-9598
Number of pages6
JournalProceedings of the National Academy of Sciences
Volume98
Issue number17
DOIs
Publication statusPublished - 2001

Fingerprint

Metallothionein
Toxicity
Zinc
Bacteria
Metals
Ligands
Sulfur
LIM Domain Proteins
Genes
Ions
Proteins
Poisons
DNA
Boats
Transcription
Histidine
Conformations

Keywords

  • metallothionein
  • zinc toxicity
  • zinc finger

Cite this

Parkinson, J.A. ; Blindauer, C.A. ; Harrison, M.D. ; Robinson, A.K. ; Turner-Cavfet, J.S. ; Robinson, N.J. ; Sadler, P.J. / A metallothionein containing a zinc finger within a four-metal cluster protects a bacterium from zinc toxicity. In: Proceedings of the National Academy of Sciences . 2001 ; Vol. 98, No. 17. pp. 9593-9598.
@article{9ba2d14d65334cadbbee173e30bd6bd7,
title = "A metallothionein containing a zinc finger within a four-metal cluster protects a bacterium from zinc toxicity",
abstract = "Zinc is essential for many cellular processes, including DNA synthesis, transcription, and translation, but excess can be toxic. A zinc-induced gene, smtA, is required for normal zinc-tolerance in the cyanobacterium Synechococcus PCC 7942. Here we report that the protein SmtA contains a cleft lined with Cys-sulfur and His-imidazole ligands that binds four zinc ions in a Zn4Cys9His2 cluster. The thiolate sulfurs of five Cys ligands provide bridges between the two ZnCys4 and two ZnCys3His sites, giving two fused six-membered rings with distorted boat conformations. The inorganic core strongly resembles the Zn4Cys11 cluster of mammalian metallothionein, despite different amino acid sequences, a different linear order of the ligands, and presence of histidine ligands. Also, SmtA contains elements of secondary structure not found in metallothioneins. One of the two Cys4-coordinated zinc ions in SmtA readily exchanges with exogenous metal (111Cd), whereas the other is inert. The thiolate sulfur ligands bound to zinc in this site are buried within the protein. Regions of β-strand and α-helix surround the inert site to form a zinc finger resembling the zinc fingers in GATA and LIM-domain proteins. Eukaryotic zinc fingers interact specifically with other proteins or DNA and an analogous interaction can therefore be anticipated for prokaryotic zinc fingers. SmtA now provides structural proof for the existence of zinc fingers in prokaryotes, and sequences related to the zinc finger motif can be identified in several bacterial genomes.",
keywords = "metallothionein , zinc toxicity , zinc finger",
author = "J.A. Parkinson and C.A. Blindauer and M.D. Harrison and A.K. Robinson and J.S. Turner-Cavfet and N.J. Robinson and P.J. Sadler",
year = "2001",
doi = "10.1073/pnas.171120098",
language = "English",
volume = "98",
pages = "9593--9598",
journal = "Proceedings of the National Academy of Sciences",
issn = "1091-6490",
number = "17",

}

A metallothionein containing a zinc finger within a four-metal cluster protects a bacterium from zinc toxicity. / Parkinson, J.A.; Blindauer, C.A.; Harrison, M.D.; Robinson, A.K.; Turner-Cavfet, J.S.; Robinson, N.J.; Sadler, P.J.

In: Proceedings of the National Academy of Sciences , Vol. 98, No. 17, 2001, p. 9593-9598.

Research output: Contribution to journalConference Contribution

TY - JOUR

T1 - A metallothionein containing a zinc finger within a four-metal cluster protects a bacterium from zinc toxicity

AU - Parkinson, J.A.

AU - Blindauer, C.A.

AU - Harrison, M.D.

AU - Robinson, A.K.

AU - Turner-Cavfet, J.S.

AU - Robinson, N.J.

AU - Sadler, P.J.

PY - 2001

Y1 - 2001

N2 - Zinc is essential for many cellular processes, including DNA synthesis, transcription, and translation, but excess can be toxic. A zinc-induced gene, smtA, is required for normal zinc-tolerance in the cyanobacterium Synechococcus PCC 7942. Here we report that the protein SmtA contains a cleft lined with Cys-sulfur and His-imidazole ligands that binds four zinc ions in a Zn4Cys9His2 cluster. The thiolate sulfurs of five Cys ligands provide bridges between the two ZnCys4 and two ZnCys3His sites, giving two fused six-membered rings with distorted boat conformations. The inorganic core strongly resembles the Zn4Cys11 cluster of mammalian metallothionein, despite different amino acid sequences, a different linear order of the ligands, and presence of histidine ligands. Also, SmtA contains elements of secondary structure not found in metallothioneins. One of the two Cys4-coordinated zinc ions in SmtA readily exchanges with exogenous metal (111Cd), whereas the other is inert. The thiolate sulfur ligands bound to zinc in this site are buried within the protein. Regions of β-strand and α-helix surround the inert site to form a zinc finger resembling the zinc fingers in GATA and LIM-domain proteins. Eukaryotic zinc fingers interact specifically with other proteins or DNA and an analogous interaction can therefore be anticipated for prokaryotic zinc fingers. SmtA now provides structural proof for the existence of zinc fingers in prokaryotes, and sequences related to the zinc finger motif can be identified in several bacterial genomes.

AB - Zinc is essential for many cellular processes, including DNA synthesis, transcription, and translation, but excess can be toxic. A zinc-induced gene, smtA, is required for normal zinc-tolerance in the cyanobacterium Synechococcus PCC 7942. Here we report that the protein SmtA contains a cleft lined with Cys-sulfur and His-imidazole ligands that binds four zinc ions in a Zn4Cys9His2 cluster. The thiolate sulfurs of five Cys ligands provide bridges between the two ZnCys4 and two ZnCys3His sites, giving two fused six-membered rings with distorted boat conformations. The inorganic core strongly resembles the Zn4Cys11 cluster of mammalian metallothionein, despite different amino acid sequences, a different linear order of the ligands, and presence of histidine ligands. Also, SmtA contains elements of secondary structure not found in metallothioneins. One of the two Cys4-coordinated zinc ions in SmtA readily exchanges with exogenous metal (111Cd), whereas the other is inert. The thiolate sulfur ligands bound to zinc in this site are buried within the protein. Regions of β-strand and α-helix surround the inert site to form a zinc finger resembling the zinc fingers in GATA and LIM-domain proteins. Eukaryotic zinc fingers interact specifically with other proteins or DNA and an analogous interaction can therefore be anticipated for prokaryotic zinc fingers. SmtA now provides structural proof for the existence of zinc fingers in prokaryotes, and sequences related to the zinc finger motif can be identified in several bacterial genomes.

KW - metallothionein

KW - zinc toxicity

KW - zinc finger

U2 - 10.1073/pnas.171120098

DO - 10.1073/pnas.171120098

M3 - Conference Contribution

VL - 98

SP - 9593

EP - 9598

JO - Proceedings of the National Academy of Sciences

T2 - Proceedings of the National Academy of Sciences

JF - Proceedings of the National Academy of Sciences

SN - 1091-6490

IS - 17

ER -