Defining the metal binding pathways of human metallothionein 1a: balancing zinc availability and cadmium seclusion

• DOI: 10.1039/c5mt00225g
• Publication Date: 2015-11-13T16:02:04Z
• Authors: Gordon W. Irvine; Tyler B. J. Pinter; Martin J. Stillman
• Keywords: Metalation; Metallothionein; Metalloprotein

Metallothioneins (MTs) are cysteine-rich, metal-binding proteins that found throughout Nature. This ubiquity highlights their importance in essential metal regulation, heavy detoxification and cellular redox chemistry. Missing from the current description of MT function is underlying mechanism by which MTs achieve proposed biological functions. To date, there have been conflicting reports on binding structures intermediates formed during metalation apoMTs. The form metal-bound dictates sequestering metal-donating properties protein. Through a detailed analysis spectral data electrospray ionization mass spectromeric circular dichroism methods we report Zn(ii) Cd(ii) human MT1a takes place through two distinct pathways. first pathway involves formation beaded with up to five metals bound terminally 20 cysteines protein via noncooperative mechanism. second dominated four-metal domain cluster structure M4SCYS11via cooperative We different preferences for apo-hMT1a. follows above pH 7.1 but beginning below clustered (Cd4Scys11) begins dominate. In contrast, terminal, "beaded", at all physiologically relevant (pH ≥ 5.2) only following 5.1. results presented here allow us reconcile concerning presence MTs. conflict regarding versus mechanisms also reconciled experimental described here. These metal-specific pathways radically intermediate provide insight into multi-functional nature MT: donation metalloenzymes toxic structure.