Experimental recombining of repetitive motifs leads to large functional metallothioneins and demonstrates their modular evolvability potential.

Protein modularity is acknowledged for promoting the emergence of new protein variants via domain rearrangements. Metallothioneins (MTs) offer an excellent model system for experimentally examining the consequences of domain rearrangements due to the possibility to assess the functional properties of native and artificially created variants using spectroscopic methods and metal tolerance assays. In this study, we have investigated the functional properties of AbiMT4 from the snail Alinda biplicata (Gastropoda, Mollusca), a large MT comprising 10 putative β domains (β3β1), alongside four artificially designed variants differing in domain number, type, or order.

A multi-domain snail metallothionein increases cadmium resistance and fitness in Caenorhabditis elegans.

Metallothioneins (MTs) are a family of mostly low-molecular weight, cysteine-rich proteins capable of specific metal-ion binding that are involved in metal detoxification and homeostasis, as well as in stress response. In contrast to most other animal species which possess two-domain (bidominial) MTs, some gastropod species have evolved Cd-selective multidomain MTs (md-MTs) consisting of several concatenated β3 domains and a single C-terminal β1 domain. Each domain contains three-metal ion clusters and binds three metal ions.

Metals and metallothionein evolution in snails: a contribution to the concept of metal-specific functionality from an animal model group.

This is a critical review of what we know so far about the evolution of metallothioneins (MTs) in Gastropoda (snails, whelks, limpets and slugs), an important class of molluscs with over 90,000 known species. Particular attention will be paid to the evolution of snail MTs in relation to the role of some metallic trace elements (cadmium, zinc and copper) and their interaction with MTs, also compared to MTs from other animal phyla. The article also highlights the important distinction, yet close relationship, between the structural and metal-selective binding properties of gastropod MTs and their physiological functionality in the living organism.

A de novo evolved domain improves the cadmium detoxification capacity of limpet metallothioneins.

Metallothioneins (MTs) constitute an important family of metal binding proteins. Mollusk MTs, in particular, have been used as model systems to better understand the evolution of their metal binding features and functional adaptation. In the present study two recombinantly produced MTs, LgiMT1 and LgiMT2, and their de novo evolved γ domain, of the marine limpet Lottia gigantea, were analyzed by electronic spectroscopy and mass spectrometry.

The Modular Architecture of Metallothioneins Facilitates Domain Rearrangements and Contributes to Their Evolvability in Metal-Accumulating Mollusks.

Protein domains are independent structural and functional modules that can rearrange to create new proteins. While the evolution of multidomain proteins through the shuffling of different preexisting domains has been well documented, the evolution of domain repeat proteins and the origin of new domains are less understood. Metallothioneins (MTs) provide a good case study considering that they consist of metal-binding domain repeats, some of them with a likely de novo origin.