Neuronal growth‐inhibitory factor (metallothionein‐3): reactivity and structure of metal–thiolate clusters*

Abstract

Metallothionein‐3, also called neuronal growth‐inhibitory factor, is one of the four members of the mammalian metallothionein family, which in turn belongs to the metallothionein, a class of ubiquitously occurring low‐molecular‐weight cysteine‐ and metal‐rich proteins containing metal–thiolate clusters. Mammalian metallothioneins contain two metal–thiolate clusters of the type M(II)3‐Cys9 and M(II)4‐Cys11 [or Cu(I)4‐CysS6‐9]. Although metallothionein‐3 shares these metal clusters with the well‐characterized metallothionein‐1 and metallothionein‐2, it shows distinct biological, structural and chemical properties. This short review focuses on the recent developments regarding the chemistry of the metal clusters in metallothionein‐3, in comparison to those in metallothionein‐1 and metallothionein‐2, and discusses the possible biological and functional implications.

Role of Zinc Metallothionein-3 (ZnMt3) in Epidermal Growth Factor (EGF)-induced c-Abl Protein Activation and Actin Polymerization in Cultured Astrocytes

“…The apo-Mt3 form (i.e. with no bound metal) is predominantly unstructured and unable to support activity; thus, the metal binding status of Mt3 is important for its biochemical and physiological activity (33). In this context, we found that removal of zinc also rendered Mt3 and peptide 1 completely incapable of promoting actin polymerization or dis- sociating c-Abl from F-actin, suggesting that zinc binding is essential for the Mt3 effects described here.…”

“…Mt3 and peptide 1 have "zinc-binding motifs" (31)(32)(33)(34). Hence, we examined whether the binding of zinc was required for the effects of Mt3 and/or peptide 1.…”

Metallothioneins and zinc in cancer diagnosis and therapy

“…MT-3 represents a unique metalloprotein called also neuronalgrowth inhibitory factor, which inhibits the outgrowth of neuronal cells (Huang, 2010). In comparison with MT-1 and MT-2, MT-3 shows distinct chemical, structural, and biological properties (Faller, 2010;Ding et al, 2010;Brewer, 2009;Bofill et al, 2009;Ba et al, 2009). Moreover, the connection of MT-3 to neurodegenerative processes is discussed.…”

Metallothionein-3 (MT-3) in the Human Adrenal Cortex and its Disorders

“…Metallothioneins (MTs) are intracellular, low molecular weight proteins containing an array of conserved 20 cysteines and polynuclear metal-sulfur coordination sites formed by metal ions [1,2]. Their most widely detected isoforms in mammals, MT-1 and MT-2, are rapidly induced in the liver by a wide range of metals, drugs, and inflammatory mediators [3].…”