Arsenic transfer between metallothionein proteins at physiological pH

As3+ bound to the two-domain, recombinant human metallothionein (isoform 1a) is stable at pH 7 and translocates via protein–protein interactions to other metallothionein proteins. The data show As3+ transfer from the two-domain β-α-hMT to binding sites in the isolated apo-β-hMT and apo-α-hMT. Under conditions of equilibrium, apo- and partially-metallated species coexist indicating that noncooperative demetallation of the As6-βα-hMT occurrs. As3+ transfer under conditions (pH 7) where the free As3+ ion is not stable, provides evidence that Cd2+ and Zn2+ transfer may also take place through protein–protein interactions and that partially metallated Cd–MT and Zn–MT would be stable.

Research highlights
► Human metallothionein 1a and the two isolated fragments bind As(III) at all pH values from 2–8.
► Electrospray ionization mass spectrometry shows retention of the structures of the As-containing metallothioneins over a wide pH range.
► The As(III) bound to the two-domain human MT is transferred directly to the one-domain, metal-free fragments at pH 7.
► Protein-protein interactions are proposed for the metal exchange reaction.
► Partially metallated forms of the one-domain and two-domain human As–MT species are formed at equilibrium.