ABSTRACT

In the last few years a considerable amount of literature has been published concern­ ing the mechanism of copper incorporation into proteins in vivo. This is a field of intense current interest, and it has now been established that a network of coppertrafficking genes is required (see, for example, [60]). The most complete picture avail­ able is that for the copper chaperones identified in cells of the yeast Saccharomyces cerevisiae. Reduction of environmental Cu(II) to Cu(I) by the FRE1 gene product appears to be the first essential step [61-63]. The copper(I) then enters the yeast cells by means of the CTR (copper transport) family of proteins [64] and is transferred to a set of copper chaperone proteins. Atxl is a 73-residue cytoplasmic protein encoded by the ATX1 gene and delivers copper to Ccc2, a membrane-bound copper transporter, for use in the maturation of Fet3 (see Chapter 16 on multi-copper oxi­ dases) in the post-Golgi vesicles. A second chaperone protein, Lys7 (also termed yCCS by Rae et al., [59] in human cells) is a 249-residue protein encoded by the LYS7 gene that delivers copper to inactive superoxide dismutase (SOD1) in the cytoplasm. Evidence has recently been provided [59,65] that Lys7 directly inserts copper into SOD1 when the intracellular copper concentration is low; it is estimated that the upper limit for the concentration of free copper is 10“8 M, equivalent to 10-9 copper atoms), so that free copper is effectively non-existent. A third chaperone protein in yeast cells, Cox 17 [66], a 69-residue protein, delivers copper to cytochrome c oxidase (CCO) in the mitochondrial intermembrane space.