Encyclopedia of Metalloproteins

2013 Edition
| Editors: Robert H. Kretsinger, Vladimir N. Uversky, Eugene A. Permyakov

Biological Copper Transport

  • David L. Huffman
  • Alia V. H. Hinz
Reference work entry
DOI: https://doi.org/10.1007/978-1-4614-1533-6_101



Biological copper transport describes the acquisition and delivery of Cu(I) to cellular destinations, as well as the removal of excess Cu(I). Eukaryotic cells transport Cu(I) via permeases, metallochaperones, Cu(I)-specific pumps, and accessory factors responsible for holoprotein maturation. Key cellular challenges include the prevention of deleterious adventitious reactions and the facile (i.e., rapid) movement of Cu(I) in transit. Inborn errors of certain genes in these pathways are linked to Wilson’s disease, Menkes disease, ALS (Lou Gehrig’s disease), and cytochrome c oxidase deficiency.

A Copper Requirement

Copper has been refined and processed by humans since the dawn of civilization but its role in living processes was only appreciated in the twentieth century. The vital processes of respiration, iron uptake, neurotransmitter synthesis, and free radical detoxification all include enzymes...

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DLH gratefully acknowledges support from the National Science Foundation (CAREER 0645518) and AVHH acknowledges Western Michigan University Graduate Student Research Fund.


  1. Banci L, Bertini I, McGreevy KS, Rosato A (2010) Molecular recognition in copper trafficking. Nat Prod Rep 27:695–710, http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20442960
  2. Boal AK, Rosenzweig AC (2009) Structural biology of copper trafficking. Chem Rev 109:4760–4779, http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19824702
  3. De Feo CJ, Aller SG, Unger VM (2007) A structural perspective on copper uptake in eukaryotes. Biometals 20:705–716, http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17211682
  4. Huffman DL, O’Halloran TV (2001) Function, structure, and mechanism of intracellular copper trafficking proteins. Annu Rev Biochem 70:677–701, http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11395420
  5. Inesi G (2011) Calcium and copper transport ATPases: analogies and diversities in transduction and signaling mechanisms. J Cell Commun Signal 5:227–237. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=21656155
  6. Kim BE, Nevitt T, Thiele DJ (2008) Mechanisms for copper acquisition, distribution and regulation. Nat Chem Biol 4:176–185, http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18277979
  7. Leitch JM, Yick PJ, Culotta VC (2009) The right to choose: multiple pathways for activating copper, zinc superoxide dismutase. J Biol Chem 284:24679–24683, http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19586921
  8. Lutsenko S, Barnes NL, Bartee MY, Dmitriev OY (2007) Function and regulation of human copper-transporting ATPases. Physiol Rev 87:1011–1046, http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17615395
  9. Robinson NJ, Winge DR (2010) Copper metallochaperones. Annu Rev Biochem 79:537–562. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20205585
  10. Xiao Z, Brose J, Schimo S, Ackland SM, La Fontaine S, Wedd AG (2011) Unification of the copper(I) binding affinities of the metallo-chaperones Atx1, Atox1, and related proteins: detection probes and affinity standards. J Biol Chem 286:11047–11055. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=21258123

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© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of ChemistryWestern Michigan UniversityKalamazooUSA