Structural domain plasticity drives Zn(II) distribution and buffering in metallothionein-3

Abstract

Complementary mass spectrometry-based approaches and molecular dynamics simulations were integrated to map Zn(II) distribution in partially metalated Zn4-6-metallothionein-3 species relevant to zinc metabolism. Sequential Zn(II) dissociation engages both the α and β domains through a structurally plastic, interdomain mechanism that underpins regulatory zinc buffering at physiological pZn.