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Evidence for non‐isostructural replacement of Zn 2+ with Cd 2+ in the β‐domain of brain‐specific metallothionein‐3

2002; Wiley; Volume: 527; Issue: 1-3 Linguagem: Inglês

10.1016/s0014-5793(02)03169-1

1873-3468

Peep Palumaa, Olga Njunkova, Lesja Pokras, Elo Eriste, Hans Jörnvall, Rannar Sillard,

Heavy Metal Exposure and Toxicity

Metallothionein‐3 (MT‐3) is a brain‐specific MT, which is downregulated in Alzheimer's disease. The N‐terminal region of CdMT‐3 is highly dynamic and has escaped structural characterization by nuclear magnetic resonance. We have used electrospray ionization mass spectrometry to probe conformational states of cadmium‐ and zinc‐substituted metalloforms of MT‐3 and can demonstrate that the N‐terminal β‐domain of MT‐3 filled with Cd 2+ has a more open conformation than that filled with Zn 2+ . The results suggest that the larger Cd 2+ ions cannot isostructurally replace zinc in the β‐domain of MT‐3 whereas in the case of MT‐1 and MT‐2 the replacement is isostructural. Specific metal binding properties of the β‐domain of MT‐3 may be essential for fulfilling the specific role of MT‐3 in the brain.