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

Proceedings of the National Academy of Sciences of the United States of America - Tập 98 Số 17 - Trang 9593-9598 - 2001
Claudia A. Blindauer1, Mark D. Harrison1, John A. Parkinson1, Andrea K. Robinson1, Jim Cavet1, Nigel J. Robinson1, Peter J. Sadler1
1Department of Chemistry, University of Edinburgh, West Mains Road, Edinburgh EH9 3JJ, United Kingdom; and Department of Biochemistry and Genetics, University of Newcastle, Newcastle NE2 4HH, United Kingdom

Tóm tắt

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 cyanobacteriumSynechococcusPCC 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 Zn4Cys9His2cluster. The thiolate sulfurs of five Cys ligands provide bridges between the two ZnCys4and two ZnCys3His sites, giving two fused six-membered rings with distorted boat conformations. The inorganic core strongly resembles the Zn4Cys11cluster 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.

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Tài liệu tham khảo

N J Robinson, A Gupta, A P Fordham-Skelton, R R D Croy, B A Whitton, J W Huckle Proc R Soc London Ser B 242, 241–247 (1990).

R W Olafson, W D McCubbin, C M Kay Biochem J 251, 691–699 (1988).

J W Huckle, A P Morby, J S Turner, N J Robinson Mol Microbiol 7, 177–187 (1993).

J S Turner, A P Morby, A B Whitton, A Gupta, N J Robinson J Biol Chem 268, 4494–4498 (1993).

A J Bird, J S Turner-Cavet, J S Lakey, N J Robinson J Biol Chem 273, 21246–21252 (1998).

M Vašák, D W Hasler Curr Opin Chem Biol 4, 177–183 (2000).

K Wüthrich Methods Enzymol 205, 502–529 (1991).

J H R Kägi Methods Enzymol 205, 613–626 (1991).

R D Palmiter Proc Natl Acad Sci USA 95, 8428–8430 (1998).

D A Suhy, K D Simon, D I H Linzer, T V O'Halloran J Biol Chem 274, 9183–9192 (1999).

G K Andrews Biochem Pharmacol 59, 95–104 (2000).

C Jacob, W Maret, B L Vallee Proc Natl Acad Sci USA 95, 3489–3494 (1998).

D F Cano-Gauci, B Sarkar FEBS Lett 386, 1–4 (1996).

M J Daniels, J S Turner-Cavet, R Selkirk, H Sun, J A Parkinson, P J Sadler, N J Robinson J Biol Chem 273, 22957–22961 (1998).

D P Higham, P J Sadler, M D Scawen Science 225, 1043–1046 (1984).

M Vašák Methods Enzymol 205, 450–458 (1991).

U Piantini, O Sørensen, R R Ernst J Am Chem Soc 104, 6800–6801 (1982).

A Bax, D G Davis J Magn Reson 65, 355–360 (1985).

A Kumar, K Wüthrich, R R Ernst Biochem Biophys Res Commun 95, 1–6 (1980).

D J States, R A Haberkorn, D J Ruben J Magn Reson 48, 286–292 (1982).

T L Hwang, A J Shaka J Magn Reson Ser A 112, 275–279 (1995).

O W Zhang, L E Kay, J P Olivier, J D Forman-Kay J Biomol NMR 4, 845–858 (1994).

H Kuboniwa, S Grzesiek, F Delaglio, A Bax J Biomol NMR 4, 871–878 (1994).

P Güntert, W Braun, K Wüthrich J Mol Biol 217, 517–530 (1991).

W Braun, G Wagner, E Wörgötter, M Vašák, J H R Kägi, K Wüthrich J Mol Biol 187, 125–129 (1986).

S S Hasnain, G P Diakun, I Abrahams, I Ross, C D Garner, I Bremner, M Vašák Experientia Suppl 52, 227–236 (1985).

S Karlin, Z-Y Zhu Proc Natl Acad Sci USA 94, 14231–14236 (1997).

R Koradi, M Billeter, K Wüthrich J Mol Graphics 14, 51–55 (1996).

G Öz, D L Pountney, I M Armitage Biochem Cell Biol 76, 223–234 (1998).

B A Messerle, A Schäffer, M Vašák, J H R Kägi, K Wüthrich J Mol Biol 225, 433–443 (1992).

G Wagner, D Neuhaus, E Wörgötter, M Vašák, J H R Kägi, K Wüthrich J Mol Biol 187, 131–135 (1986).

P Schultze, E Wörgötter, M Vašák, J H R Kägi, K Wüthrich J Mol Biol 203, 251–268 (1988).

Y Umezawa, S Tsuboyama, H Takahashi, J Usawa, M Nishio Bioorg Med Chem 7, 2021–2026 (1999).

I Rayment, G Wesenberg, T E Meyer, M A Cusanovich, H M Holden J Mol Biol 228, 672–686 (1992).

R Marmorstein, M Carey, M Ptashne, S C Harrison Nature (London) 356, 408–414 (1992).

M Vašák, C E McClelland, H A O Hill, J H R Kägi Experientia 41, 30–34 (1985).

M Vašák, J H R Kägi Metal Ions Biol Syst 15, 213–273 (1983).

Y Zhou, N Zhang, L Li, B Ru Protein Peptide Lett 7, 9–16 (2000).

B A Krizek, D L Merkle, J M Berg Inorg Chem 32, 937–940 (1993).

D G Nettesheim, H R Engeseth, J D Otvos Biochemistry 24, 6744–6751 (1985).

J G Omichinski, G M Clore, O Schaad, G Felsenfeld, C Trainor, E Appella, S J Stahl, A M Gronenborn Science 261, 438–446 (1993).

X Yao, G C Perez-Alvaro, H A Louis, P Pomies, C Hatt, M F Summers, M C Beckerle Biochemistry 38, 5701–5713 (1999).

A Velyvis, Y Yang, C Wu, J Qin J Biol Chem 276, 4932–4939 (2001).

A Y Chou, J Archdeacon, C I Kado Proc Natl Acad Sci USA 95, 5293–5298 (1998).

N Bouhouche, M Syvanen, C I Kado Trends Microbiol 8, 77–81 (2000).

S A Wolfe, L Nekludova, C O Pablo Annu Rev Biophys Biomol Struct 3, 183–212 (1999).

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Thông tin xuất bản

Proceedings of the National Academy of Sciences of the United States of America

Tập 98 Số 17

9593-9598

Thông tin tác giả