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

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Abstract

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. ZnII, CdII, CuI) 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 YC[C with combining low line]xxC motif, that is altered to YC[S with combining low 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.

Graphical abstract: Impact of naturally occurring serine/cysteine variations on the structure and function of Pseudomonas metallothioneins

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Publication details

The article was received on 29 Aug 2019, accepted on 21 Oct 2019 and first published on 15 Nov 2019


Article type: Paper
DOI: 10.1039/C9MT00213H
Metallomics, 2019, Advance Article
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    Impact of naturally occurring serine/cysteine variations on the structure and function of Pseudomonas metallothioneins

    J. Habjanič, S. Chesnov, O. Zerbe and E. Freisinger, Metallomics, 2019, Advance Article , DOI: 10.1039/C9MT00213H

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