Protein classification is a handy tool to characterise freshly discovered proteins. By comparing their three-dimensional structure with other well-known proteins, their function may be proposed. However, the function of metallothioneins (MTs), which are a group of cysteine-rich proteins with high coordinating capacity, is quite challenging to determine. This is mainly consequence of their labile 3D-structure, which is modulated by the metal cluster associated to the protein. These proteins are physiologically found wrapping clusters of several metal ions and each metal-MT association has a variable stability, which means that each polypeptide sequence has specific affinities for each kind of metal. By characterising the biochemical properties of these metal-MT complexes, it is possible to make assumptions about MTs' biological functions. Besides, it is straightforward to assume that if an MT builds a stable metal cluster with a certain metal ion, its function will relate to a biological function involving that metal ion. Based on that, our group designed a method to aid in the prediction of MTs' function by classifying them by their metal-binding abilities, separating those that show high affinity when rendering complexes of divalent metal ions (Zn-thioneins) and those that display high stability in association with monovalent metal clusters (Cu-thioneins), considering all the intermediate steps between them. Then, this criterion perfectly differentiates between these two extreme behaviours, however, due to the chemical similarities of Zn and Cd, their interaction with MTs in most of the cases barely differ between them and, thus, it has never been contemplated the existence of two different metal-binding behaviours specific for each metal ion. It is the research performed over decades that permitted to gather some cases of MTs with differential selectivity towards Cd(II) ions and lead us to consider the possibility to separate the current Zn-thioneins group into Zn- and Cd-thioneins. To demonstrate that, this PhD thesis has been devoted to characterising several examples of MTs, revealing that each of the two metal-binding behaviours hypothesised display differential traits. Thanks to the data and discussion presented here it has been possible to update the dichotomic MT classification (Zn- to Cu-thioneins) into a three-band classification (Zn-, Cd and Cu-thioneins). We anticipate that this work will allow to advance into the research of MTs and the pursuit of the finding of their functions.
Updating the current dichotomic ''I'' classification of metallothioneins to a new ''Y'' setting: Differentiation between genuine Zn- and Cd-thioneins
Garcia Risco Aguado, M. E. (Author). 7 Apr 2022
Student thesis: Doctoral thesis
Student thesis: Doctoral thesis