Copper Transporters and Chaperones

Abstract

Copper is an essential element for many cellular processes in all the kingdoms of life. Its presence in cells needs to be tightly controlled, as free copper ions can be toxic due to their redox chemistry, though they must be available to obtain the mature form of copper‐dependent proteins. For this purpose, organisms have developed a machinery for proteins, which control copper uptake, transport, sequestration, and efflux. These proteins are engaged in complex, highly specific pathways, responsible for copper incorporation in target proteins, its transport within a compartment and/or through different cellular compartments and organelles, and its excretion. In the present chapter, we describe the structural and functional features of proteins involved in the three most characterized processes, that is, copper delivery to the trans‐Golgi network or transport across the plasma membrane, involving copper‐transporting adenosine triphosphatases, copper incorporation into the Cu,Zn superoxide dismutase, and into the two copper centers of cytochrome c oxidase, located in two different enzyme subunits and involving three copper ions. The structural properties of various functional states of these copper transport proteins, and the related mechanisms, are discussed with respect to their key role in cellular processes.

Asymmetric Catalysis Mediated by Synthetic Peptides, Version 2.0: Expansion of Scope and Mechanisms

“…Within this protein, a short sequence of eight residues called Mets7 was known to bind well to Cu(I) and Pt(II). 485 Recognizing this, Rimoldi and co-workers examined the efficacy of Mets7-Cu complexes as Lewis acid catalysts for Henry (nitroaldol) reactions of benzaldehyde 11.58 with nitromethane 11.59 (Figure 217). 486 Native peptide 11.61a was found to adopt two major conformations using MD simulations, both of which were consistent with β-turn motifs (Figure 217b).…”

Ligand Noninnocence of Thiolate/Disulfide in Dinuclear Copper Complexes: Solvent-Dependent Redox Isomerization and Proton-Coupled Electron Transfer

“…Highly specific, sulfur-rich proteins ( e .g., Atx1, Cox17, Sco1, CCS, metallothioneins) transport copper (Cu), an essential cofactor for many enzymes, to cellular targets with tight control. − The most common mechanism of transport is nucleophilic attack by an apoprotein thiol on a S–Cu I –S donor, but a small number of processes may use the redox flexibility of cysteine residues for function. , For example, a Cu thiolate/disulfide interconversion in human Sco1 is hypothesized as one potential mechanism for Cu delivery to the Cu A site of cytochrome c oxidase. − Disulfide bond formation is essential for the activity of Cu–Zn superoxide dismutase (SOD1) and is accelerated greatly in the presence of O 2 and Cu–CCS, its copper chaperone, potentially via Cu(II) formed by aerobic oxidation of Cu(I) . Cu thiolate/disulfide interconversions may also operate in malfunctioning living systems to prevent aberrant reactive oxygen species (ROS) production by Cu .…”

"Platinum on the road": Interactions of antitumoral cisplatin with proteins

“…A few predicted Cu binding residues, including at least one conserved cysteine residue, are present in these domains [48]. Chaperones can then deliver Cu to other proteins which use it directly (superoxide dismutase) or bring it to subcellular districts such as the mitochondrion (where it is taken up by cytochrome c oxidase) or to the Golgi (where it is taken up by ceruloplasmin, an iron oxidase) [49].…”