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

摘要

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 beta-domain (residues 1-32) and the alpha-domain (residues 3268) 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 Cd-113 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 Cd-113(7)-GIF. The structural studies suggest the existence of distinct (Me4S11)-S-II and (Me3S9)-S-II clusters located in the mutually interacting alpha- and beta-domains, respectively, of Cd-7-GIF. In addition, evidence for a highly dynamic and flexible structure of this protein is presented. (C)2000 Elsevier Science Inc. All rights reserved. [References: 19]