Reversible folding of cysteine-rich metallothionein by an overcritical reaction path

Yi Liang Liu, Hui Ting Lee, Chia-Ching Chang, Lou Sing Kan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


A first-order-like state transition is considered to be involved in the restoration of the activities of a few proteins by correctly folding the protein [Phys. Rev. E 66 (2002) 021903]. In order to understand the general applicability of this mechanism, we studied a metallothionein (MT) protein with an unconventional structure, i.e., without any α-helix or β-sheet. MT is a 61 amino-acid peptide. There are 6-7 Zn2+ ions, which bind avidly to 20 conserved cysteines (Cys) of MT. These properties indicate that the structure of MT is quite different from those of the other proteins. Similar to our previous findings, the denatured MT can be folded without any aggregation via a designated stepwise quasi-static process (an over-critical reaction path). The particle size of folded MT intermediates, determined by dynamic light scattering, shrank right after the first folding stage. It is consistent with a collapse-model. In addition, results from both atomic absorption and circular dichroism (CD) indicate that the stable intermediates may fold to the native conformation but with only partial Zn2+ binding, which in turn implies that those folding intermediates are in a molten globular state. These reversible unfolding and folding processes indicate that Cys-rich protein, MT, may also be folded by way of a first-order-like state transition mechanism. We suspect that this process may likely be involved in the reaction of the metal substitution process in metal containing enzymes.

Original languageEnglish
Pages (from-to)59-63
Number of pages5
JournalBiochemical and Biophysical Research Communications
Issue number1
StatePublished - 20 Jun 2003


  • Atomic absorption
  • Circular dichroism
  • First-order-like state transition
  • Folding
  • Metallothionein
  • Quasi-static process

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