Metal-thiolate clusters in neuronal growth inhibitory factor (GIF).

Abstract Human neuronal growth inhibitory factor (GIF) is a metallothionein-like protein specific to the central nervous system, which has been linked to Alzheimer’s disease. In this article a short overview of the biological and structural properties of native Cu 4 ,Zn 3 -GIF are described. Moreover, metal-thiolate clusters formed in the synthetic β-domain (residues 1–32) and the α-domain (residues 32–68) both with native Cu I and Zn II , and as a spectroscopic probe also with Cd(II) are discussed. The cluster formation was followed by electronic absorption, circular dichroism (CD), magnetic circular dichroism (MCD) and 113 Cd NMR spectroscopy and, in the special case of Cu(I) complexes, by luminescence spectroscopy at 77 K. These structural features are compared with those of recombinant Zn 7 - and 113 Cd 7 -GIF. The structural studies suggest the existence of distinct Me II 4 S 11 and Me II 3 S 9 clusters located in the mutually interacting α- and β-domains, respectively, of Cd 7 -GIF. In addition, evidence for a highly dynamic and flexible structure of this protein is presented.