Evidence for non‐isostructural replacement of Zn2+ with Cd2+ in the β‐domain of brain‐specific metallothionein‐3

FEBS Letters

Pokras, Lesja¹  Njunkova, Olga¹  Eriste, Elo²  Palumaa, Peep¹  Jörnvall, Hans²  Sillard, Rannar² 

[1] Centre for Gene Technology, Tallinn Technical University, Ehitajate tee 5, EE-19086 Tallinn, Estonia;Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden

关键词: Metallothionein-3;    Growth inhibitory factor;    Charge state distribution analysis;    Electrospray ionization time of flight mass spectrometry;    Conformation of clusters;    MT;    metallothionein;    NMR;    nuclear magnetic resonance;    DTT;    1;    4-dithiothreitol;    ESI TOF MS;    electrospray ionization time of flight mass spectrometry;   

DOI  :  10.1016/S0014-5793(02)03169-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 Cd²⁺ has a more open conformation than that filled with Zn²⁺. The results suggest that the larger Cd²⁺ 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.

【 授权许可】

Unknown