Cd2+‐ or Hg2+‐binding proteins can replace the Cu+‐chaperone Atx1 in delivering Cu+ to the secretory pathway in yeast

Abstract
Copper delivery to Ccc2 – the Golgi Cu+‐ATPase – was investigated in vivo, replacing the Cu+‐chaperone Atx1 by various structural homologues in an atx1Δ yeast strain. Various proteins, displaying the same ferredoxin‐like fold and (M/L)(T/S)CXXC metal‐binding motif as Atx1 and known as Cu+‐, Cd2+‐ or Hg2+‐binding proteins were able to replace Atx1. Therefore, regardless of their original function, these proteins could all bind copper and transfer it to Ccc2, suggesting that Ccc2 is opportunistic and can interact with many different proteins to gain Cu+. The possible role of electrostatic potential surfaces in the docking of Ccc2 with these Atx1‐homologues is discussed.