An Integrated Mass Spectrometry and Molecular Dynamics Simulations Approach Reveals the Spatial Organization Impact of Metal-Binding Sites on the Stability of Metal-Depleted Metallothionein-2 Species.

ABSTRACT: Mammalian metallothioneins (MTs) are a group of cysteine-rich proteins that bind metal ions in two α- and β-domains and represent a major cellular Zn(II)/Cu(I) buffering system in the cell. At cellular free Zn(II) concentrations (10^-11-10^-9 M), MTs do not exist in fully loaded forms with seven Zn(II)-bound ions (Zn₇MTs). Instead, MTs exist as partially metal-depleted species (Zn_4-6MT) because their Zn(II) binding affinities are on the nano- to picomolar range comparable to the concentrations of cellular Zn(II). The mode of action of MTs remains poorly understood, and thus, the aim of this study is to characterize the mechanism of Zn(II) (un)binding to MTs, the thermodynamic properties of the Zn_1-6MT2 species, and their mechanostability

SUBMITTER: Peris-Diaz MD 

PROVIDER: S-EPMC8517974 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature