Cyclic AMP-dependent protein kinase controls energy interconversion during the catalytic cycle of the yeast copper-ATPase.
The pathogenesis of human Menkes and Wilson diseases depends on alterations in copper transport. Some reports suggest that intracellular traffic of copper might be regulated by kinase-mediated phosphorylation. However, there is no evidence showing the influence of kinase-related processes in coupled ATP hydrolysis/copper transport cycles. Here, we show that cyclic AMP-dependent protein kinase (PKA) regulates Ccc2p, the yeast Cu(I)-ATPase, with PKA-mediated phosphorylation of a conserved serine (Ser258) being crucial for catalysis. Long-range intramolecular communication between Ser258 and Asp627 (at the catalytic site) modulates the key pumping event: the conversion of the high-energy to the low-energy phosphorylated intermediate associated with copper release.
Valverde
Rafael H F
RH
Laboratório de Físico-Química Biológica, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal de Rio de Janeiro, 21949-900 Rio de Janeiro, Brazil.
Morin
Isabelle
I
Lowe
Jennifer
J
Mintz
Elisabeth
E
Cuillel
Martine
M
Vieyra
Adalberto
A
D000595:Amino Acid Sequence; D001216:Asparagine / Q000378:metabolism; D002384:Catalysis; D020134:Catalytic Domain / Q000235:genetics; D027682:Cation Transport Proteins / Q000378:metabolism*; D003300:Copper / Q000494:pharmacology; D000079922:Copper Transport Proteins; D054751:Cyclic AMP-Dependent Protein Kinase Catalytic Subunits / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D012694:Serine / Q000235:genetics / Q000378:metabolism*
C092974:CCC2 protein, S cerevisiae; D027682:Cation Transport Proteins; D000079922:Copper Transport Proteins; D029701:Saccharomyces cerevisiae Proteins; D012694:Serine; D001216:Asparagine; D003300:Copper; D054751:Cyclic AMP-Dependent Protein Kinase Catalytic Subunits