title: Chemical foundation of the attenuation of methylmercury(II) cytotoxicity by metallothioneins.
abstract: To elucidate the chemical interactions underlying the role of metallothioneins (MTs) in reducing the cytotoxicity caused by MeHg(II), we monitored in parallel by electronic absorption and CD spectroscopies the stepwise addition of MeHgCl stock solution to mammalian Zn(7)-MT1 and the isolated Zn(4)-alphaMT1 and Zn(3)-betaMT1 fragments. The incorporation of MeHg(+) into Zn(7)-MT and Zn(3)-betaMT entails total displacement of Zn(II) and unfolding of the protein. However, both features are only partial for Zn(4)-alphaMT. The different behavior observed for this fragment, whether isolated or constituting one of the two domains of Zn(7)-MT, indicates interdomain interactions in the whole protein. Overall, the binding properties of Zn(7)-MT, Zn(4)-alphaMT and Zn(3)-betaMT toward MeHg(+) are unprecedented. In addition, the sequestration of MeHg(+) by Zn(7)-MT and the concomitant release of Zn(II) are probably two of the main contributions in the detoxifying role of mammalian MT.
authors.affiliation: Departament de Química, Facultat de Ciències, Universitat Autònoma de Barcelona, Spain.
authors.forename: Angels
authors.initials: A
authors.lastname: Leiva-Presa
authors.forename: Mercè
authors.initials: M
authors.lastname: Capdevila
authors.forename: Neus
authors.initials: N
authors.lastname: Cols
authors.forename: Silvia
authors.initials: S
authors.lastname: Atrian
authors.forename: Pilar
authors.initials: P
authors.lastname: González-Duarte
mesh_terms: D000818:Animals; D002942:Circular Dichroism; D004583:Electrons; D005285:Fermentation; D007477:Ions; D008667:Metalloproteins; D008668:Metallothionein / Q000737:chemistry*; D008767:Methylmercury Compounds / Q000494:pharmacology*; D017434:Protein Structure, Tertiary; D013053:Spectrophotometry; D014466:Ultraviolet Rays; D015032:Zinc / Q000737:chemistry
chemical_list: D007477:Ions; D008667:Metalloproteins; D008767:Methylmercury Compounds; D008668:Metallothionein; D015032:Zinc