title: The isolated Cys2His2 site in EC metallothionein mediates metal-specific protein folding.
abstract: The selectivity of proteins involved in metal ion homeostasis is an important part of the puzzle to understand how cells allocate the correct metal ions to the correct proteins. Due to their similar ligand-binding properties, and their frequent co-existence in soils, essential zinc and toxic cadmium are a particularly challenging couple. Thus, minimisation of competition of Cd(2+) for Zn(2+) sites is of crucial importance for organisms that are in direct contact with soil. Amongst these, plants have an especially critical role, due to their importance for nutrition and energy. We have studied an embryo-specific, zinc-binding metallothionein (E(C)) from wheat by nuclear magnetic resonance, electrospray mass spectrometry, site-directed mutagenesis, and molecular modelling. Wheat E(C) exploits differences in affinities of Cys(4) and Cys(2)His(2) sites for Cd(2+) and Zn(2+) to achieve metal-selective protein folding. We propose that this may constitute a novel mechanism to discriminate between essential Zn(2+) and toxic Cd(2+).
authors.affiliation: Department of Chemistry, University of Warwick, Coventry, UK CV4 7AL.
authors.forename: Oksana Iryna
authors.initials: OI
authors.lastname: Leszczyszyn
authors.forename: Craig Roy J
authors.initials: CR
authors.lastname: White
authors.forename: Claudia Andrea
authors.initials: CA
authors.lastname: Blindauer
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002104:Cadmium / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008668:Metallothionein / Q000737:chemistry* / Q000378:metabolism*; D008670:Metals / Q000378:metabolism*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010940:Plant Proteins / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017510:Protein Folding; D017433:Protein Structure, Secondary; D021241:Spectrometry, Mass, Electrospray Ionization; D014908:Triticum / Q000378:metabolism; D015032:Zinc / Q000378:metabolism
chemical_list: D008670:Metals; D010940:Plant Proteins; D002104:Cadmium; D008668:Metallothionein; D015032:Zinc