Impact of naturally occurring serine/cysteine variations on the structure and function of metallothioneins

• Published in: Metallomics 2020-01, Vol.12 (1), p.23-33
• Main Authors: Habjani, Jelena, Chesnov, Serge, Zerbe, Oliver, Freisinger, Eva
• Format: Article
• ISSN: 1756-5901; 1756-591X
• DOI: 10.1039/c9mt00213h

Metallothioneins (MTs), small cysteine-rich metal-binding proteins, support the viability of organisms under normal physiological conditions and help them to respond to different environmental stressors. Upon metal coordination ( e.g. Zn II , Cd II , Cu I ) they form characteristic polynuclear metal-thiolate clusters that are known for their high thermodynamic stability and kinetic lability. However, despite numerous studies, it is still not understood how MTs modulate their metal-binding properties. Pseudomonas MTs are an emerging subclass of bacterial MTs, distinct for their high number of His residues and for several unique features such as an intrinsically disordered long C-terminal tail and multiple variations in the number and nature of coordinating amino acids. These variations might provide the bacteria with a functional advantage derived from evolutionary adaptation to heterogeneous environments. Nearly 90% of the known Pseudomonas MT sequences feature a central YCC&cmb.b.line;xxC motif, that is altered to YCS&cmb.b.line;xxC in the rest. We demonstrate that the additional Cys residue serves as a coordinating ligand without influencing the metal-binding capacity, the overall metal-binding stability or the structure. However, the additional ligand changes intra-cluster dynamics and, as a consequence, modulates metal transfer reactions that could be functionally advantageous in vivo . Naturally occurring Ser/Cys variations in Pseudomonas metallothioneinss affect intra-cluster dynamics rather than binding capacity.