title: Unexpected Interactions of the Cyanobacterial Metallothionein SmtA with Uranium.
abstract: Molecules for remediating or recovering uranium from contaminated environmental resources are of high current interest, with protein-based ligands coming into focus recently. Metallothioneins either bind or redox-silence a range of heavy metals, conferring protection against metal stress in many organisms. Here, we report that the cyanobacterial metallothionein SmtA competes with carbonate for uranyl binding, leading to formation of heterometallic (UO2)(n)Zn4SmtA species, without thiol oxidation, zinc loss, or compromising secondary or tertiary structure of SmtA. In turn, only metalated and folded SmtA species were found to be capable of uranyl binding. (1)H NMR studies and molecular modeling identified Glu34/Asp38 and Glu12/C-terminus as likely adventitious, but surprisingly strong, bidentate binding sites. While it is unlikely that these interactions correspond to an evolved biological function of this metallothionein, their occurrence may offer new possibilities for designing novel multipurpose bacterial metallothioneins with dual ability to sequester both soft metal ions including Cu(+), Zn(2+), Cd(2+), Hg(2+), and Pb(2+) and hard, high-oxidation state heavy metals such as U(VI). The concomitant protection from the chemical toxicity of uranium may be valuable for the development of bacterial strains for bio-remediation.
authors.affiliation: Molecular Biology Division, Bhabha Atomic Research Centre , Trombay, Mumbai, India.
authors.forename: Celin
authors.initials: C
authors.lastname: Acharya
authors.affiliation: Department of Chemistry, University of Warwick , Coventry, United Kingdom.
authors.forename: Claudia A
authors.initials: CA
authors.lastname: Blindauer
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry*; D002942:Circular Dichroism; D000458:Cyanobacteria / Q000737:chemistry*; D004591:Electrophoresis, Polyacrylamide Gel; D008668:Metallothionein / Q000737:chemistry*; D015394:Molecular Structure; D066244:Proton Magnetic Resonance Spectroscopy; D021241:Spectrometry, Mass, Electrospray Ionization; D014501:Uranium / Q000737:chemistry*
chemical_list: D001426:Bacterial Proteins; C080048:smtA protein, Synechococcus; D014501:Uranium; D008668:Metallothionein