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

Human neuronal growth inhibitory factor (GIF) is a metallothionein-like pro tein specific to the central nervous system, which has been linked to Alzhe imer's disease. In this article a short overview of the biological and stru ctural properties of native Cu-4,Zn-3-GIF are described. Moreover, metal-th iolate clusters formed in the synthetic beta-domain (residues 1-32) and the alpha-domain (residues 3268) both with native Cu-I and Zn-II, and as a spe ctroscopic probe also with Cd(II) are discussed. The cluster formation was followed by electronic absorption, circular dichroism (CD), magnetic circul ar dichroism (MCD) and Cd-113 NMR spectroscopy and, in the special case of Cu(I) complexes, by luminescence spectroscopy at 77 K. These structural fea tures are compared with those of recombinant Zn-7- and Cd-113(7)-GIF. The s tructural studies suggest the existence of distinct (Me4S11)-S-II and (Me3S 9)-S-II clusters located in the mutually interacting alpha- and beta-domain s, respectively, of Cd-7-GIF. In addition, evidence for a highly dynamic an d flexible structure of this protein is presented. (C)2000 Elsevier Science Inc. All rights reserved.