Copper transport in mammalian cells: special care for a metal with special needs

Abstract

Copper plays an essential role in human physiology. It is required for respiration, radical defense, neuronal myelination, angiogenesis, and many other processes. Copper has distinct physicochemical properties that pose uncommon challenges for its transport across biological membranes. Only small amounts of copper are present in biological fluids, and essentially none of it exists in a free ion form. These properties and the low redox potential of copper dictate special structural and mechanistic features in copper transporters. This minireview discusses molecular mechanisms through which copper enters and exits human cells.

FIGURE 1.

Copper transport in enterocytes. Copper is shown to enter the enterocyte from the blood via hCTR1 and from the intestine through an unidentified mechanism. Copper then binds to copper chaperones, which deliver it to the target proteins, including ATP7A and ATP7B. CTR1 and CTR2 may also be involved in copper release from the intracellular vesicles. TGN, trans-Golgi network.

FIGURE 2.

Structural model of hCTR1 from De Feo et al. (15) and the hypothetical structure of human Cu-ATPase based on the structure of archaeal CopA from Wu et al. (31) and modeling predictions for the N-terminal MBS1–4 (gray). The A-domain (yellow) and N- and P-domains (green) interact with the MBS in the N-terminal domain (purple and gray).