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.
metabolism
Female
Biophysical Phenomena
DNA
Copper
Cation Transport Proteins
Adenosine Triphosphatases
Humans
Protein Conformation
Placenta
metabolism
Pregnancy
Two-Hybrid System Techniques
Hydrolysis
metabolism
chemistry
Cytoplasm
Adenosine Triphosphate
Golgi Apparatus
metabolism
Catalysis
chemistry
chemistry
chemistry
Complementary
Mutation
Author
Pernilla Wittung Stafshede
Chalmers, Biology and Biological Engineering, Chemical Biology
Quarterly Reviews of Biophysics
0033-5835 (ISSN) 1469-8994 (eISSN)
Vol. 48 4 471-8Subject Categories (SSIF 2011)
Biochemistry and Molecular Biology
Biological Sciences
Biophysics
DOI
10.1017/S0033583515000128
PubMed
26537407