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
00335835 (ISSN) 14698994 (eISSN)
Vol. 48 4 471-8Subject Categories
Biochemistry and Molecular Biology
Biological Sciences
Biophysics
DOI
10.1017/S0033583515000128
PubMed
26537407