Structural Adaptation of a Protein to Increased Metal Stress: NMR Structure of a Marine Snail Metallothionein with an Additional Domain

In this study, we present an NMR structure of the metallothionein (MT) from the snail Littorina littorea (LlMT) in complex with Cd2+. LlMT is capable of binding 9 Zn2+ or 9 Cd2+ ions. Sequence alignments with other snail MTs revealed that the protein is likely composed of three domains. The study revealed that the protein is divided into three individual domains, each of which folds into a single well-defined threemetal cluster. The central alpha 2 and C-terminal b domains are positioned with a unique relative orientation. Two variants with longer and shorter linkers were investigated, which revealed that specific interdomain contacts only occurred with the wildtype linker. Moreover, a domain-swap mutant in which the highly similar alpha 1 and alpha 2 domains were exchanged was structurally almost identical. It is suggested that the expression of a three-domain MT confers an evolutionary advantage on Littorina littorea in terms of coping with Cd2+ stress and adverse environmental conditions.