Interaction of metal ions with glutaminase interacting protein (GIP): A potential role of GIP in brain diseases
Issue title: From Molecule to Tissue: XII European Conference on the Spectroscopy of Biological Molecules, Bobigny, France, 1–6 September 2007, Part 2 of 2
Affiliations: Department of Chemistry and Biochemistry, Auburn University, Auburn, AL, USA
Note: [] Corresponding author: Assoc. Prof. Smita Mohanty, PhD, Department of Chemistry and Biochemistry, 179 Chemistry Building, Auburn University, Auburn, AL 36849-5312, USA. Tel.: +1 334 844 7081; Fax: +1 334 844 4089; E-mail: [email protected].
Abstract: Glutaminase interacting protein (GIP), a PDZ domain containing protein, mediates the distribution and clustering of proteins/peptides in membranes, acting as a scaffold where signaling molecules are linked to a multi-protein complex. GIP has been shown to play a key role in the glutamate signaling system. Some metals, particularly Pb2+, Cu2+ and Zn2+, have been implicated in a wide range of neurological disorders including Alzheimer's disease and Parkinson's disease, whose etiologies have been associated with dysfunction of the glutamate signaling system. Here, for the first time, the effects of lead, copper, and zinc on GIP were determined by using circular dichroism and fluorescence spectroscopy. All three metal ions significantly affected the conformational properties of GIP. The deconvolution of CD data showed that, with increasing amounts of Pb2+/Cu2+/Zn2+, the α-helix percentage decreased while the β-sheet content increased. The binding constants of GIP to Pb2+, Cu2+ and Zn2+ determined by fluorescence were found to be 1.4, 2.38 and 2.85 μM respectively, which indicated strong bindings between GIP and all three metal ions. We propose that the metal ion binding site of GIP is located on α-2 helix, where residues His90, Asp91 and Arg94 may coordinate the metal ions. The conformational change of GIP upon metal ion binding possibly results from the disruption of a salt bridge between Asp91 and Arg94.
Keywords: GIP, PDZ domain, brain diseases, metal ions interaction, fluorescence, CD
DOI: 10.3233/SPE-2008-0345
Journal: Spectroscopy, vol. 22, no. 4, pp. 213-221, 2008
