Copper Metallochaperones

Abstract

The current state of knowledge on how copper metallochaperones support the maturation of cuproproteins is reviewed. Copper is needed within mitochondria to supply the CuA and intramembrane CuB sites of cytochrome oxidase, within the trans-Golgi network to supply secreted cuproproteins and within the cytosol to supply superoxide dismutase 1 (Sod1). Subpopulations of copper-zinc superoxide dismutase also localize to mitochondria, the secretory system, the nucleus and, in plants, the chloroplast, which also requires copper for plastocyanin. Prokaryotic cuproproteins are found in the cell membrane and in the periplasm of gram-negative bacteria. Cu(I) and Cu(II) form tight complexes with organic molecules and drive redox chemistry, which unrestrained would be destructive. Copper metallochaperones assist copper in reaching vital destinations without inflicting damage or becoming trapped in adventitious binding sites. Copper ions are specifically released from copper metallochaperones upon contact with their cognate cuproproteins and metal transfer is thought to proceed by ligand substitution.

Periplasmic proteins encoded by VCA0261–0260 and VC2216 genes together with copA and cueR products are required for copper tolerance but not for virulence in Vibrio cholerae

“…In fact, one of the least studied aspects of the transport mechanism of Cu + -ATPases is how the ion is released from the intramembrane metal-binding site into the periplasm (Barry et al, 2011;Raimunda et al, 2011). However, copper might not be found free in the periplasm and periplasmic copper chaperones have been described by Kim et al (2010) and Robinson & Winge (2010). Thus, according to our results, the function of CopG in the periplasm may be closely related to that of CopA.…”

Biometals and Their Therapeutic Implications in Alzheimer's Disease

“…This is important because copper is increased in amyloid; however, copper levels are decreased in AD neuronal tissue [77], which could deprive copper-binding proteins such as superoxide dismutase and ceruloplasmin of the metal, which can impair their function. Superoxide dismutase is a major copper binding protein and antioxidant in neurons, which utilizes copper to convert the superoxide free radical into hydrogen peroxide [167]. Ceruloplasmin is another major copper-binding protein, which functions as a ferroxidase to promote iron export [168,169].…”

Comparison of global responses to mild deficiency and excess copper levels in Arabidopsis seedlings

“…15 Moreover, COPT5 is involved in the mobilisation of Cu from the lumen of the vacuole or prevacuolar compartments towards the cytosol in response to extreme Cu-deficient conditions. 16,17 Other components in the Cu homeostasis network are soluble cytosolic cuprochaperones, 18 one of their tasks is to provide Cu to cytosolic targets, such as the CCS cuprochaperone, which delivers Cu to the Cu and zinc (Zn) superoxide dismutase (Cu/ ZnSOD). ATX1 is another cuprochaperone that delivers Cu to the P-type ATPases of Cu + (Cu + -ATPases) at the endoplasmic reticulum to pump Cu into the lumen, where it is loaded into cuproproteins in the secretory pathway.…”