Histidine ligands in bacterial metallothionein enhance cluster stability

The cyanobacterial metallothionein (MT) SmtA is the prototype for bacterial MTs and protects against elevated levels of zinc. In contrast to mammalian MTs, bacterial MTs coordinate to metal ions not only via cysteine sulfurs, but unusually for MTs, also via histidine nitrogens. To investigate whethe...

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Bibliographic Details
Published in:Journal of biological inorganic chemistry 2007-03, Vol.12 (3), p.393-405
Main Authors: Blindauer, Claudia A, Razi, M Tahir, Campopiano, Dominic J, Sadler, Peter J
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Bacteria
Bacterial Proteins - chemistry
Bacterial Proteins - genetics
Cadmium - chemistry
Cyanobacteria
Cysteine - chemistry
Cysteine - genetics
Electrostatic properties
Histidine
Histidine - chemistry
Histidine - genetics
Ions
Ligands
Metal ions
Metallothionein
Metallothionein - chemistry
Metallothionein - genetics
Molecular Sequence Data
Mutagenesis, Site-Directed
Mutation
Protein Conformation
Protein Folding
Sequence Homology, Amino Acid
Static Electricity
Sulfur
Synechococcus
Zinc - chemistry
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Summary:The cyanobacterial metallothionein (MT) SmtA is the prototype for bacterial MTs and protects against elevated levels of zinc. In contrast to mammalian MTs, bacterial MTs coordinate to metal ions not only via cysteine sulfurs, but unusually for MTs, also via histidine nitrogens. To investigate whether histidine coordination in these metal-sulfur clusters provides advantages over S-coordination only, we mutated the two metal-binding histidine residues in the cyanobacterial MT SmtA from Synechococcus PCC7942 to cysteines. We show that the mutant proteins are still capable of binding up to four zinc ions as is the wild-type protein. However, the mutations perturb protein folding and metal-binding dynamics. Interestingly, several homologues of SmtA also show variations in these two residues. We conclude that histidine residues in Synechococcus PCC7942 SmtA have a stabilising effect due to electrostatic interactions that impact on protein folding and metal cluster charge, and are involved in fine-tuning the reactivity of the bound metal ions.
ISSN:0949-8257
1432-1327
DOI:10.1007/s00775-006-0196-4