title: Structure of the actuator domain from the Archaeoglobus fulgidus Cu(+)-ATPase.
abstract: Copper homeostasis is maintained in part by membrane-bound P(1B)-type ATPases that are found in all organisms and drive the transport of this essential, yet toxic, metal ion across cellular membranes. CopA from Archaeoglobus fulgidus is a hyperthermophilic member of this ATPase subfamily and is homologous to the human Wilson and Menkes disease ATPases. To gain insight into Cu(+)-ATPase function, the structure of the CopA actuator domain (A-domain) was determined to 1.65 A resolution. The CopA A-domain functions to couple ATP hydrolysis in the ATP binding domain (ATPBD) with structural rearrangements of critical transmembrane segments. Its fold is quite similar to that of the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA1) A-domain, with the exception of an external loop region. On the basis of sequence and structural comparisons, specific residues that probably interact with the CopA ATPBD have been identified. Comparisons to the Wilson and Menkes disease A-domains reveal the presence of an additional loop that may be associated with regulatory functions in eukaryotic Cu(+)-ATPases. Finally, several mutations in the Wilson and Menkes disease ATPases occur in the A-domain, and their likely effects on function can be inferred from the CopA A-domain structure.
authors.affiliation: Department of Biochemistry, Northwestern University, Evanston, Illinois 60208, USA.
authors.forename: Matthew H
authors.initials: MH
authors.lastname: Sazinsky
authors.forename: Sorabh
authors.initials: S
authors.lastname: Agarwal
authors.forename: José M
authors.initials: JM
authors.lastname: Argüello
authors.forename: Amy C
authors.initials: AC
authors.lastname: Rosenzweig
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry* / Q000378:metabolism*; D019611:Archaeoglobus fulgidus / Q000201:enzymology*; D001483:Base Sequence; D001665:Binding Sites; D001692:Biological Transport; D027682:Cation Transport Proteins / Q000737:chemistry* / Q000378:metabolism*; D003300:Copper / Q000378:metabolism; D000073840:Copper-Transporting ATPases; D006527:Hepatolenticular Degeneration / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006868:Hydrolysis; D007706:Menkes Kinky Hair Syndrome / Q000378:metabolism / Q000473:pathology; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D020539:Sequence Analysis, Protein
chemical_list: D027682:Cation Transport Proteins; D003300:Copper; D000251:Adenosine Triphosphatases; D000073840:Copper-Transporting ATPases