Solution structure and intermolecular interactions of the third metal-binding domain of ATP7A, the Menkes disease protein.
The third metal-binding domain of the human Menkes protein (MNK3), a copper(I)-transporting ATPase, has been expressed in Escherichia coli and characterized in solution. The solution structure of MNK3, its copper(I)-binding properties, and its interaction with the physiological partner, HAH1, have been studied. MNK3 is the domain most dissimilar in structure from the other domains of the Menkes protein. This is reflected in a significant rearrangement of the last strand of the four-stranded beta-sheet when compared with the other known homologous proteins or protein domains. MNK3 is also peculiar with respect to its interaction with the copper(I) ion, as it was found to be a comparatively weak binder. Copper(I) transfer from metal-loaded HAH1 was observed experimentally, but the metal distribution was shifted toward binding by HAH1. This is at variance with what is observed for the other Menkes domains.
Banci
Lucia
L
Magnetic Resonance Center (CERM), University of Florence, Via L. Sacconi 6, 50019 Sesto Fiorentino, Italy.
Bertini
Ivano
I
Cantini
Francesca
F
DellaMalva
Nunzia
N
Herrmann
Torsten
T
Rosato
Antonio
A
Wüthrich
Kurt
K
D000251:Adenosine Triphosphatases / Q000737:chemistry*; D027682:Cation Transport Proteins / Q000737:chemistry*; D003300:Copper / Q000737:chemistry / Q000378:metabolism; D000073840:Copper-Transporting ATPases; D004247:DNA / Q000737:chemistry; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D007706:Menkes Kinky Hair Syndrome / Q000378:metabolism; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
D027682:Cation Transport Proteins; D003300:Copper; D004247:DNA; D000251:Adenosine Triphosphatases; C081184:ATP7A protein, human; D000073840:Copper-Transporting ATPases