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

ABSTRACT: 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.

SUBMITTER: Yu CH

PROVIDER: S-EPMC5766562 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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

Yu Corey H CH Lee Woonghee W Nokhrin Sergiy S Dmitriev Oleg Y OY

Scientific reports 20180112 1

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 repo ...[more]

PMID: 29330485

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