The crystal structures of a copper-bound metallochaperone from Saccharomyces cerevisiae

Atx1 is a metallochaperone protein from the yeast Saccharomyces cerevisiae (yAtx1) that plays a major role in copper homeostasis in this organism. yAtx1 functions as a copper transfer protein by shuttling copper to the secretory pathway to control intracellular copper levels. Here we describe the first crystal structures of yAtx1 that have been determined in the presence of Cu(I). The structures from two different crystal forms have been solved and refined to resolutions of 1.65 and 1.93Å. In contrast to the previous metallated crystal structure of yAtx1 where a single Hg(II) atom was coordinated by one yAtx1 molecule, the Cu(I)-yAtx1 was crystallised as a dimer in both crystal forms, sharing one Cu(I) atom between two yAtx1 molecules. This is consistent with the crystal structure of the human homologue Cu(I)-hAtox1. Overall the structures in the two different crystal forms of Cu(I)-yAtx1 are remarkably similar to that of Cu(I)-hAtox1. However, subtle structural differences between Cu(I)-yCtr1 and Cu(I)-hAtox1 are observed in copper coordination geometries and in the conformations of Loop 2, with the latter potentially contributing to differential interactions and copper transfer mechanisms with membrane transport copper uptake systems.