Metallothionein diversity and distribution in the tree of life: a multifunctional protein

MTs are small cysteine-rich proteins that chelate metal ions such as Cu + and Zn 2+ , and are widely distributed in several life domains, in particular the eukaryotic one. They are present in the following phyla: Opisthokonta (mainly Fungi and Metazoa ), Chloroplastida , Alveolata (ciliates) and Excavata ( Trichomonas ) for Eukaryota and Cyanobacteria , Actinobacteria , Proteobacteria and Firmicutes for Bacteria . However, their absence in some phyla underlines that MTs are far from being fully known. The MT amino acid sequences show a great diversity of sizes and structures both in terms of cysteine motifs and organization of these motifs. This review also highlights the different oxidized, apoprotein and metalated forms of MTs, the diversity of interactions they can establish with different molecules and their central and multifunctional cellular role. We present MTs as a protein system that could be a hub in molecular interaction networks. Studying MTs as a hub in cellular interaction networks should provide new insights for a better understanding of MT functioning and cellular processes. Metallothioneins are diverse, but not represented yet in all phyla. Moreover, they play a central role as a [MT:T:TO] protein system.