Structure of a copper pump suggests a regulatory role for its metal-binding domain.
P-type ATPases play an important role in Cu homeostasis, which provides sufficient Cu for metalloenzyme biosynthesis but prevents oxidative damage of free Cu to the cell. The P(IB) group of P-type ATPases includes ATP-dependent pumps of Cu and other transition metal ions, and it is distinguished from other family members by the presence of N-terminal metal-binding domains (MBD). We have determined structures of two constructs of a Cu pump from Archaeoglobus fulgidus (CopA) by cryoelectron microscopy of tubular crystals, which reveal the overall architecture and domain organization of the molecule. By comparing these structures, we localized its N-terminal MBD within the cytoplasmic domains that use ATP hydrolysis to drive the transport cycle. We have built a pseudoatomic model by fitting existing crystallographic structures into the cryoelectron microscopy maps for CopA, which suggest a Cu-dependent regulatory role for the MBD.
Skirball Institute of Biomolecular Medicine, School of Medicine, New York University, 540 First Avenue, New York, NY 10016, USA.
Chen-Chou
CC
Wu
William J
WJ
Rice
David L
DL
Stokes
D000251:Adenosine Triphosphatases / Q000737:chemistry*; D019843:Archaeal Proteins / Q000737:chemistry*; D019611:Archaeoglobus fulgidus; D027682:Cation Transport Proteins / Q000737:chemistry*; D003300:Copper / Q000737:chemistry*; D000073840:Copper-Transporting ATPases; D020285:Cryoelectron Microscopy; D003460:Crystallization; D007091:Image Processing, Computer-Assisted; D008958:Models, Molecular; D017434:Protein Structure, Tertiary
D019843:Archaeal Proteins; D027682:Cation Transport Proteins; D003300:Copper; D000251:Adenosine Triphosphatases; D000073840:Copper-Transporting ATPases