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Please use this identifier to cite or link to this item: http://hdl.handle.net/2262/40229

Title: The neuronal adaptor protein X11alpha interacts with the copper chaperone for SOD1 and regulates SOD1 activity.
Author: MC LOUGHLIN, DECLAN
Sponsor: Wellcome Trust
Author's Homepage: http://people.tcd.ie/mclougde
Keywords: Neuroscience
X11 alpha protein
Issue Date: 2001
Publisher: American Society for Biochemistry and Molecular Biology
Citation: McLoughlin, DM, Standen, CL, Lau, KF, Ackerley, S, Bartnikas, TP, Gitlin, JD, Miller, CC, The neuronal adaptor protein X11alpha interacts with the copper chaperone for SOD1 and regulates SOD1 activity., The Journal of Biological Chemistry, 276, 12, 2001, 9303 - 9307
Series/Report no.: The Journal of Biological Chemistry;
276;
12;
Abstract: The neuronal adaptor protein X11a participates in the formation of multiprotein complexes and intracellular trafficking. It contains a series of discrete protein-protein interaction domains including two contiguous Cterminal PDZ domains. We used the yeast two-hybrid system to screen for proteins that interact with the PDZ domains of human X11a, and we isolated a clone encoding domains II and III of the copper chaperone for Cu,Zn-superoxide dismutase-1 (CCS). The X11a/CCS interaction was confirmed in coimmunoprecipitation studies plus glutathione S-transferase fusion protein pull-down assays and was shown to be mediated via PDZ2 of X11a and a sequence within the carboxyl terminus of domain III of CCS. CCS delivers the copper cofactor to the antioxidant superoxide dismutase-1 (SOD1) enzyme and is required for its activity. Overexpression of X11a inhibited SOD1 activity in transfected Chinese hamster ovary cells which suggests that X11a binding to CCS is inhibitory to SOD1 activation. X11a also interacts with another copper-binding protein found in neurons, the Alzheimer’s disease amyloid precursor protein. Thus, X11a may participate in copper homeostasis within neurons.
Description: PUBLISHED
URI: http://hdl.handle.net/2262/40229
Related links: http://dx.doi.org/10.1074/jbc.M010023200
Appears in Collections:Psychiatry (Scholarly Publications)

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