The growth inhibitory activity of metallothionein-3 correlates with its novel β domain sequence rather than metal binding properties

Abstract

A neuronal survival assay consisting of cultured neonatal rat cortical neurons supplemented with Alzheimer brain extracts was used to identify a protein designated growth inhibitory factor (GIF) as a candidate growth inhibitory component in normal brain tissue [1]. Subsequent characterization of GIF revealed a 70% sequence homology with mammalian metallothionein (MT) including the 20 metal-binding cysteine residues in conserved Cys-X-Cys and Cys-X-XCys motifs. The GIF gene also has a similar intron/exon structure to that of mammalian MT-1 and MT-2 leading to its classification as MT-3 [2]. Relative to mammalian MTs, MT-3 contains two inserts, a single threonine residue in the N-terminal β-domain and a glutamine rich hexapeptide in the C-terminal α-domain.