title: Copper binding triggers compaction in N-terminal tail of human copper pump ATP7B.
abstract: Protein conformational changes are fundamental to biological reactions. For copper ion transport, the multi-domain protein ATP7B in the Golgi network receives copper from the cytoplasmic copper chaperone Atox1 and, with energy from ATP hydrolysis, moves the metal to the lumen for loading of copper-dependent enzymes. Although anticipated, conformational changes involved in ATP7B's functional cycle remain elusive. Using spectroscopic methods we here demonstrate that the four most N-terminal metal-binding domains in ATP7B, upon stoichiometric copper addition, adopt a more compact arrangement which has a higher thermal stability than in the absence of copper. In contrast to previous reports, no stable complex was found in solution between the metal-binding domains and the nucleotide-binding domain of ATP7B. Metal-dependent movement of the first four metal-binding domains in ATP7B may be a trigger that initiates the overall catalytic cycle.
authors.affiliation: Chemistry Department, Umeå University, 90187 Umeå, Sweden.
authors.forename: Tanumoy
authors.initials: T
authors.lastname: Mondol
authors.affiliation: Chemistry Department, Umeå University, 90187 Umeå, Sweden.
authors.forename: Jörgen
authors.initials: J
authors.lastname: Åden
authors.affiliation: Biology and Biological Engineering Department, Chalmers University of Technology, 41296 Gothenburg, Sweden. Electronic address: Pernilla.wittung@chalmers.se.
authors.forename: Pernilla
authors.initials: P
authors.lastname: Wittung-Stafshede
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry* / Q000648:ultrastructure*; D001665:Binding Sites; D027682:Cation Transport Proteins / Q000737:chemistry* / Q000648:ultrastructure*; D003198:Computer Simulation; D003300:Copper / Q000737:chemistry*; D000073840:Copper-Transporting ATPases; D004789:Enzyme Activation; D008956:Models, Chemical; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
chemical_list: D027682:Cation Transport Proteins; D003300:Copper; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases
keywords: Circular dichroism; Conformational changes; Copper transport; Metalloenzymes; NMR; Protein–protein interactions