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The Structure of Metal Binding Domain 1 of the Copper Transporter ATP7B Reveals Mechanism of a Singular Wilson Disease Mutation

Copper-transporter ATP7B maintains copper homeostasis in the human cells and delivers copper to the biosynthetic pathways for incorporation into the newly synthesized copper-containing proteins. ATP7B is a target of several hundred mutations that lead to Wilson disease, a chronic copper toxicosis. A...

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Autores principales: Yu, Corey H., Lee, Woonghee, Nokhrin, Sergiy, Dmitriev, Oleg Y.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5766562/
https://www.ncbi.nlm.nih.gov/pubmed/29330485
http://dx.doi.org/10.1038/s41598-017-18951-1
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author Yu, Corey H.
Lee, Woonghee
Nokhrin, Sergiy
Dmitriev, Oleg Y.
author_facet Yu, Corey H.
Lee, Woonghee
Nokhrin, Sergiy
Dmitriev, Oleg Y.
author_sort Yu, Corey H.
collection PubMed
description Copper-transporter ATP7B maintains copper homeostasis in the human cells and delivers copper to the biosynthetic pathways for incorporation into the newly synthesized copper-containing proteins. ATP7B is a target of several hundred mutations that lead to Wilson disease, a chronic copper toxicosis. ATP7B contains a chain of six cytosolic metal-binding domains (MBDs), the first four of which (MBD1-4) are believed to be regulatory, and the last two (MBD5-6) are required for enzyme activity. We report the NMR structure of MBD1, the last unsolved metal-binding domain of ATP7B. The structure reveals the disruptive mechanism of G85V mutation, one of the very few disease causing missense mutations in the MBD1-4 region of ATP7B.
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spelling pubmed-57665622018-01-17 The Structure of Metal Binding Domain 1 of the Copper Transporter ATP7B Reveals Mechanism of a Singular Wilson Disease Mutation Yu, Corey H. Lee, Woonghee Nokhrin, Sergiy Dmitriev, Oleg Y. Sci Rep Article Copper-transporter ATP7B maintains copper homeostasis in the human cells and delivers copper to the biosynthetic pathways for incorporation into the newly synthesized copper-containing proteins. ATP7B is a target of several hundred mutations that lead to Wilson disease, a chronic copper toxicosis. ATP7B contains a chain of six cytosolic metal-binding domains (MBDs), the first four of which (MBD1-4) are believed to be regulatory, and the last two (MBD5-6) are required for enzyme activity. We report the NMR structure of MBD1, the last unsolved metal-binding domain of ATP7B. The structure reveals the disruptive mechanism of G85V mutation, one of the very few disease causing missense mutations in the MBD1-4 region of ATP7B. Nature Publishing Group UK 2018-01-12 /pmc/articles/PMC5766562/ /pubmed/29330485 http://dx.doi.org/10.1038/s41598-017-18951-1 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Yu, Corey H.
Lee, Woonghee
Nokhrin, Sergiy
Dmitriev, Oleg Y.
The Structure of Metal Binding Domain 1 of the Copper Transporter ATP7B Reveals Mechanism of a Singular Wilson Disease Mutation
title The Structure of Metal Binding Domain 1 of the Copper Transporter ATP7B Reveals Mechanism of a Singular Wilson Disease Mutation
title_full The Structure of Metal Binding Domain 1 of the Copper Transporter ATP7B Reveals Mechanism of a Singular Wilson Disease Mutation
title_fullStr The Structure of Metal Binding Domain 1 of the Copper Transporter ATP7B Reveals Mechanism of a Singular Wilson Disease Mutation
title_full_unstemmed The Structure of Metal Binding Domain 1 of the Copper Transporter ATP7B Reveals Mechanism of a Singular Wilson Disease Mutation
title_short The Structure of Metal Binding Domain 1 of the Copper Transporter ATP7B Reveals Mechanism of a Singular Wilson Disease Mutation
title_sort structure of metal binding domain 1 of the copper transporter atp7b reveals mechanism of a singular wilson disease mutation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5766562/
https://www.ncbi.nlm.nih.gov/pubmed/29330485
http://dx.doi.org/10.1038/s41598-017-18951-1
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