Unresolved questions in human copper pump mechanisms.
Journal article, 2015

Copper (Cu) is an essential transition metal providing activity to key enzymes in the human body. To regulate the levels and avoid toxicity, cells have developed elaborate systems for loading these enzymes with Cu. Most Cu-dependent enzymes obtain the metal from the membrane-bound Cu pumps ATP7A/B in the Golgi network. ATP7A/B receives Cu from the cytoplasmic Cu chaperone Atox1 that acts as the cytoplasmic shuttle between the cell membrane Cu importer, Ctr1 and ATP7A/B. Biological, genetic and structural efforts have provided a tremendous amount of information for how the proteins in this pathway work. Nonetheless, basic mechanistic-biophysical questions (such as how and where ATP7A/B receives Cu, how ATP7A/B conformational changes and domain-domain interactions facilitate Cu movement through the membrane, and, finally, how target polypeptides are loaded with Cu in the Golgi) remain elusive. In this perspective, unresolved inquiries regarding ATP7A/B mechanism will be highlighted. The answers are important from a fundamental view, since mechanistic aspects may be common to other metal transport systems, and for medical purposes, since many diseases appear related to Cu transport dysregulation.

Golgi Apparatus

Humans

metabolism

Adenosine Triphosphatases

Placenta

Protein Conformation

Adenosine Triphosphate

Biophysical Phenomena

Cytoplasm

chemistry

metabolism

chemistry

metabolism

Female

Catalysis

DNA

Complementary

metabolism

Hydrolysis

Pregnancy

Copper

chemistry

Cation Transport Proteins

Two-Hybrid System Techniques

chemistry

Mutation

Author

Pernilla Wittung Stafshede

Umeå University

Quarterly Reviews of Biophysics

0033-5835 (ISSN) 1469-8994 (eISSN)

Vol. 48 4 471-8

Subject Categories

Biochemistry and Molecular Biology

Biological Sciences

Biophysics

DOI

10.1017/S0033583515000128

PubMed

26537407

More information

Latest update

6/12/2019