Dynamics of interdomain and intermolecular interactions in mammalian metallothioneins

Klaus Zangger, Ian M. Armitage

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


The structures of mammalian metallothioneins (MTs), as solved by X-ray crystallography and NMR spectroscopy, all show seven divalent metals bound in two separate domains. The marked differences in metal-mobilities found for the two domains has led to the proposal for a dual role for the two MT metal domains. The tight metal binding in the C-terminal α-domain supposedly constitutes the basis for the detoxification of excess heavy metals, while the more labile metals in the N-terminal β-domain function in the homeostasis of the essential elements zinc and copper. In this overview, we compare the two types of dimers found for MTs and their influence on metal-mobilities. In the presence of excess metal, the N-terminal domain is responsible for the formation of metal-bridged dimers while under aerobic conditions, a specific intermolecular disulfide is formed between the C-terminal domains. Both forms of dimers not only involve different domains for their intermolecular protein interactions, they also exhibit radical differences in the reactive properties of their respective cluster bound metal ions. Since the metal exchange within each domain is also influenced by interdomain interactions, the relative orientation of the domains is also most likely important for MT functions. Thus far, the relative orientation of the two domains could only be obtained from the crystal structure. Here, we present evidence for increased mobility in the linker region as the reason for the lack of interdomain constraints in the solution NMR studies of mammalian MTs.

Original languageEnglish (US)
Pages (from-to)135-143
Number of pages9
JournalJournal of Inorganic Biochemistry
Issue number2
StatePublished - Jan 15 2002

Bibliographical note

Funding Information:
Partial support of this work comes from the NIH grant DK18778 to I.M.A.. K.Z. thanks the Austrian Academy of Sciences for an APART (Austrian Programme for Advanced Research and Technology) Fellowship.


  • Cd NMR
  • Dimerization
  • Dynamics
  • Metallothionein
  • NMR spectroscopy


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