Journal Article

Characterization of the Menkes Protein Copper-Binding Domains and Their Role in Copper-Induced Protein Relocalization

Ian D. Goodyer, Emma E. Jones, Anthony P. Monaco and Michael J. Francis

in Human Molecular Genetics

Volume 8, issue 8, pages 1473-1478
Published in print August 1999 | ISSN: 0964-6906
Published online August 1999 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/8.8.1473
Characterization of the Menkes Protein Copper-Binding Domains and Their Role in Copper-Induced Protein Relocalization

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Menkes disease is a fatal X-linked disorder of copper metabolism. The gene defective in Menkes disease (ATP7A) encodes a copper transporting P-type ATPase (MNK or ATP7A) with six copper-binding domains at its N-terminus. MNK is normally localized to the trans-Golgi network in cultured cells, but relocates to the plasma membrane in the presence ofelevated extracellular copper. In this study, the role of the six copper-binding domains on copper-induced redistribution is investigated. In a recombinant clone, when all the wild-type copper-binding motifs are mutated from GMX-CXXC to GMXSXXS and the cells grown in medium containing elevated copper, relocalization of the recombinant protein to the plasma membrane was not observed. Using the same assay with any one of the six copper-binding domains intact, MNK moves to the plasma membrane in a way indistinguishable from the wild-type protein. Therefore, the copper-binding domains are vital for MNK trafficking and only a single domain is sufficient for this redistribution to occur.

Journal Article.  5188 words.  Illustrated.

Subjects: Genetics and Genomics

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