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A Luminal Loop of Wilson Disease Protein Binds Copper and Is Required for Protein Activity

A Luminal Loop of Wilson Disease Protein Binds Copper and Is Required for Protein Activity

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KÖHN, Birgit, Kumaravel PONNANDAI SHANMUGAVEL, Min WU, Michael KOVERMANN, Pernilla WITTUNG-STAFSHEDE, 2018. A Luminal Loop of Wilson Disease Protein Binds Copper and Is Required for Protein Activity. In: Biophysical journal. 115(6), pp. 1007-1018. ISSN 0006-3495. eISSN 1542-0086. Available under: doi: 10.1016/j.bpj.2018.07.040

@article{Kohn2018-09-18Lumin-44419, title={A Luminal Loop of Wilson Disease Protein Binds Copper and Is Required for Protein Activity}, year={2018}, doi={10.1016/j.bpj.2018.07.040}, number={6}, volume={115}, issn={0006-3495}, journal={Biophysical journal}, pages={1007--1018}, author={Köhn, Birgit and Ponnandai Shanmugavel, Kumaravel and Wu, Min and Kovermann, Michael and Wittung-Stafshede, Pernilla} }

<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bibo="http://purl.org/ontology/bibo/" xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#" xmlns:foaf="http://xmlns.com/foaf/0.1/" xmlns:void="http://rdfs.org/ns/void#" xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > <rdf:Description rdf:about="https://kops.uni-konstanz.de/rdf/resource/123456789/44419"> <dc:contributor>Wu, Min</dc:contributor> <dc:rights>terms-of-use</dc:rights> <dc:language>eng</dc:language> <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/29"/> <dcterms:rights rdf:resource="https://kops.uni-konstanz.de/page/termsofuse"/> <dcterms:issued>2018-09-18</dcterms:issued> <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2019-01-07T10:43:55Z</dc:date> <dc:creator>Wittung-Stafshede, Pernilla</dc:creator> <dcterms:title>A Luminal Loop of Wilson Disease Protein Binds Copper and Is Required for Protein Activity</dcterms:title> <dc:creator>Kovermann, Michael</dc:creator> <dcterms:abstract xml:lang="eng">The copper-transporting ATPase ATP7B is essential for loading of copper ions to copper-dependent enzymes in the secretory pathway; its inactivation results in Wilson disease. In contrast to copper-ion uptake by the cytoplasmic domains, ATP7B-mediated copper-ion release in the Golgi has not been explored yet. We demonstrate here that a luminal loop in ATP7B, rich in histidine/methionine residues, binds reduced copper (Cu(I)) ions, and identified copper-binding residues play an essential role in ATP7B-mediated metal ion release. NMR experiments on short-peptide models demonstrate that three methionine and two histidine residues are specifically involved in Cu(I) ion binding; with these residues replaced by alanines, no Cu(I) ion interaction is detected. Although more than one Cu(I) ion can interact with the wild-type peptide, removing either all histidine or all methionine residues reduces the stoichiometry to one Cu(I) ion binding per peptide. Using a yeast complementation assay, we show that for efficient copper transport by full-length ATP7B, the complete set of histidine and methionine residues in the lumen loop are required. The replacement of histidine/methionine residues by alanines does not perturb overall ATP7B structure, as the localization of ATP7B variants in yeast cells matches that of the wild-type protein. Thus, in similarity to ATP7A, ATP7B also appears to have a luminal "exit" copper ion site.</dcterms:abstract> <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/> <dc:creator>Köhn, Birgit</dc:creator> <dc:contributor>Köhn, Birgit</dc:contributor> <dc:contributor>Wittung-Stafshede, Pernilla</dc:contributor> <foaf:homepage rdf:resource="http://localhost:8080/jspui"/> <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/44419/1/Koehn_2-14ggsx2jn8tfh6.pdf"/> <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/44419/1/Koehn_2-14ggsx2jn8tfh6.pdf"/> <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/44419"/> <dc:creator>Wu, Min</dc:creator> <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/29"/> <dc:creator>Ponnandai Shanmugavel, Kumaravel</dc:creator> <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2019-01-07T10:43:55Z</dcterms:available> <dc:contributor>Kovermann, Michael</dc:contributor> <dc:contributor>Ponnandai Shanmugavel, Kumaravel</dc:contributor> </rdf:Description> </rdf:RDF>

Dateiabrufe seit 07.01.2019 (Informationen über die Zugriffsstatistik)

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