Structure and Function of Copper Uptake Transporters

Rate and Regulation of Copper Transport by Human Copper Transporter 1 (hCTR1)

“…4 and 5). The elevated rate of copper transport in the AAA mutant as well as in truncation mutants of the hCTR1 C-terminal tail was unexpected, given previous speculation that the HCH motif is essential in permeation (16,24,38). Our results are incompatible with an essential role of the terminal three amino acids HCH in copper permeation, and instead imply that the highly conserved C-terminal tail and HCH putative metal-binding motif play a different role, perhaps as a plug or a valve at the exit site, transiently halting or slowing the progress of permeation out of the pore.…”

“…The Roles of Intracellular hCTR1 Residues in Copper Permeation-Previous lines of evidence suggest that the pore formed by hCTR1 trimers allows the permeation of Cu ϩ ions by a series of ligand-exchange reactions as the metal ion passes through rings of stabilizing methionine residues, Met-150 and Met-154, on the extracellular side of hCTR1 (16,38). Entry is presumably followed by membrane permeation via coordinating steps with intra-pore residues and subsequent delivery to an intracellular acceptor (14,38).…”

“…Entry is presumably followed by membrane permeation via coordinating steps with intra-pore residues and subsequent delivery to an intracellular acceptor (14,38). We characterized several mutants on the intracellular side of hCTR1 that elevate both the rate and the K m value of copper transport.…”

Cellular glutathione plays a key role in copper uptake mediated by human copper transporter 1

“…Transport does not appear to require ATP or to be coupled to an ion gradient (27), leaving open the question of what drives the permeation of the metal across the plasma membrane. It is generally thought that cuprous (Cu ϩ ), rather than cupric (Cu 2ϩ ) copper ions are transported by hCTR1 (40). Of numerous metals tested, only monovalent silver (Ag ϩ ) inhibits or competes with 64 Cu uptake (27), and it was subsequently shown that hCTR1 transports Ag ϩ (8).…”

Function and Regulation of the Plant COPT Family of High-Affinity Copper Transport Proteins

“…Numerous studies on yeasts, mammals, insects, algae, and plants have revealed that eukaryotes utilize the conserved CTR/COPT family of proteins to facilitate highaffinity ( = 1-5 M) cellular Cu acquisition at the plasma membrane and Cu mobilization from intracellular storage organelles, when Cu bioavailability decreases [30][31][32][33][34][35]. CTR/COPT proteins are highly specific for Cu + transport (and the isoelectric Ag + ), but not for Cu 2+ [13,36,37].…”