Nucleotide recognition by CopA, a Cu+-transporting P-type ATPase

Heavy metal pumps constitute a large subgroup in P-type ion-transporting ATPases. One of the outstanding features is that the nucleotide binding N-domain lacks residues critical for ATP binding in other well-studied P-type ATPases. Instead, they possess an HP-motif and a Glyrich sequence in the N-domain, and their mutations impair ATP binding. Here, we describe 1.85 angstrom resolution crystal structures of the P- and N-domains of CopA, an archaeal Cu+-transporting ATPase, with bound nucleotides. These crystal structures show that CopA recognises the adenine ring completely differently from other P- type ATPases. The crystal structure of the His462Gln mutant, in the HP-motif, a disease-causing mutation in human Cu+-ATPases, shows that the Gln side chain mimics the imidazole ring, but only partially, explaining the reduction in ATPase activity. These crystal structures lead us to propose a role of the His and a mechanism for removing Mg2+ from ATP before phosphoryl transfer. The EMBO Journal (2009) 28, 1782-1791. doi:10.1038/emboj.2009.143; Published online 28 May 2009