title: Evidence for non-isostructural replacement of Zn(2+) with Cd(2+) in the beta-domain of brain-specific metallothionein-3.
abstract: 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 beta-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 beta-domain of MT-3 whereas in the case of MT-1 and MT-2 the replacement is isostructural. Specific metal binding properties of the beta-domain of MT-3 may be essential for fulfilling the specific role of MT-3 in the brain.
authors.affiliation: Centre for Gene Technology, Tallinn Technical University, Ehitajate tee 5, EE-19086, Tallinn, Estonia. peepp@staff.ttu.ee
authors.forename: Peep
authors.initials: P
authors.lastname: Palumaa
authors.forename: Olga
authors.initials: O
authors.lastname: Njunkova
authors.forename: Lesja
authors.initials: L
authors.lastname: Pokras
authors.forename: Elo
authors.initials: E
authors.lastname: Eriste
authors.forename: Hans
authors.initials: H
authors.lastname: Jörnvall
authors.forename: Rannar
authors.initials: R
authors.lastname: Sillard
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002104:Cadmium / Q000737:chemistry / Q000378:metabolism*; D000090023:Metallothionein 3; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011817:Rabbits; D012996:Solutions; D021241:Spectrometry, Mass, Electrospray Ionization; D015032:Zinc / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000090023:Metallothionein 3; D009419:Nerve Tissue Proteins; D012996:Solutions; D002104:Cadmium; D015032:Zinc