American Society for Biochemistry and Molecular Biology
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
The Journal of Biological Chemistry; 276; 12;
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
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