Metallothionein in Antarctic Fish
Vincenzo Carginale\ Antonio Capasso\ Clemente Capasso!, Peter Kille 2 ,
Elio Parisi!, Gianluca L. Passaretti!, Guido di Prisco!, Marilisa Riggio!,
and Rosaria Scudiero!
!Institute of Protein Biochemistry and Enzymology, CNR, Via Marconi 12,
80125 Napoli, Italy
2School of Molecular and Medical Biosciences, University of Wales, Cardiff,
UK
Introduction
Zinc occupies a prominent position among transition and d 10 elements
because of the role played in many biological processes [1,2], including
catalysis [3], transcription and translation [4]. The functional role of zinc
depends on the large variety of metallorganic complexes produced by this
element as a result of its interaction with different protein families [3,5].
Although the existence of cellular mechanisms for absorption, secretion
and distribution of zinc have been inferred [6,7], very little is known
about regulation of zinc metabolism. Increasing evidences suggest that
metallothioneins (MTs), i.e. low-molecular weight cysteine-rich metalbinding proteins, play an important role in zinc homeostasis [8,9]. In
addition, these proteins are supposed to have also a potential role in
attenuating the cytotoxic effects caused by heavy metals and superoxide
radicals [10,11].
The understanding of the biological function of MT relies mostly on its
molecular features. Mammalian MTs are single chain proteins usually
made of 60 amino acids, including 20 cysteines with no histidine and
aromatic residues; all the cysteines are in a reduced form and engaged in
the binding of 7 equivalents of metal ions through metal-thiolate bonds
[12]. As each metal ion is tetrahedrally coordinated, some cysteines are
bridged with adjacent metal ions to form metal-thiolate clusters arranged
in two distinct domains: the N-terminus beta domain of three-metal
clusters having a cyclohexane-like structure, and the C-terminus alpha
domain of four-metal clusters having a bicyclononane-like structure
[13,14].
Both X-ray diffraction [13] and two dimensional NMR [14] studies
revealed the dynamic structure of MT which allows a rapid exchange of
metals within clusters and between MT and other proteins. These features
G. di Prisco, E. Pisano, A. Clarke (Eds)
Fishes of Antarctica. A biological overview
© Springer-Verlag Italia 1998
Vincenzo Carginale\ Antonio Capasso\ Clemente Capasso!, Peter Kille 2 ,
Elio Parisi!, Gianluca L. Passaretti!, Guido di Prisco!, Marilisa Riggio!,
and Rosaria Scudiero!
!Institute of Protein Biochemistry and Enzymology, CNR, Via Marconi 12,
80125 Napoli, Italy
2School of Molecular and Medical Biosciences, University of Wales, Cardiff,
UK
Introduction
Zinc occupies a prominent position among transition and d 10 elements
because of the role played in many biological processes [1,2], including
catalysis [3], transcription and translation [4]. The functional role of zinc
depends on the large variety of metallorganic complexes produced by this
element as a result of its interaction with different protein families [3,5].
Although the existence of cellular mechanisms for absorption, secretion
and distribution of zinc have been inferred [6,7], very little is known
about regulation of zinc metabolism. Increasing evidences suggest that
metallothioneins (MTs), i.e. low-molecular weight cysteine-rich metalbinding proteins, play an important role in zinc homeostasis [8,9]. In
addition, these proteins are supposed to have also a potential role in
attenuating the cytotoxic effects caused by heavy metals and superoxide
radicals [10,11].
The understanding of the biological function of MT relies mostly on its
molecular features. Mammalian MTs are single chain proteins usually
made of 60 amino acids, including 20 cysteines with no histidine and
aromatic residues; all the cysteines are in a reduced form and engaged in
the binding of 7 equivalents of metal ions through metal-thiolate bonds
[12]. As each metal ion is tetrahedrally coordinated, some cysteines are
bridged with adjacent metal ions to form metal-thiolate clusters arranged
in two distinct domains: the N-terminus beta domain of three-metal
clusters having a cyclohexane-like structure, and the C-terminus alpha
domain of four-metal clusters having a bicyclononane-like structure
[13,14].
Both X-ray diffraction [13] and two dimensional NMR [14] studies
revealed the dynamic structure of MT which allows a rapid exchange of
metals within clusters and between MT and other proteins. These features
G. di Prisco, E. Pisano, A. Clarke (Eds)
Fishes of Antarctica. A biological overview
© Springer-Verlag Italia 1998