Metallothioneins: unparalleled diversity in structures and functions for metal ion homeostasis and more

Metallothioneins have been the subject of intense study for five decades, and have greatly inspired the development of bio-analytical methodologies including multi-dimensional and multi-nuclear NMR. With further advancements in molecular biology, protein science, and instrumental techniques, recent years have seen a renaissance of research into metallothioneins. The current report focuses on in vitro studies of so-called class II metallothioneins from a variety of phyla, highlighting the diversity of metallothioneins in terms of structure, biological functions, and molecular functions such as metal ion specificity, thermodynamic stabilities, and kinetic reactivity. We are still far from being able to predict any of these properties, and further efforts will be required to generate the knowledge that will enable a better understanding of what governs the biological and chemical properties of these unusual and intriguing small proteins.