Chemical foundation of the attenuation of methylmercury(II) cytotoxicity by metallothioneins.
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.
Leiva-Presa
Angels
A
Departament de Química, Facultat de Ciències, Universitat Autònoma de Barcelona, Spain.
Capdevila
Mercè
M
Cols
Neus
N
Atrian
Silvia
S
González-Duarte
Pilar
P
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
D007477:Ions; D008667:Metalloproteins; D008767:Methylmercury Compounds; D008668:Metallothionein; D015032:Zinc