Solution structure and backbone dynamics of the Cu(I) and apo forms of the second metal-binding domain of the Menkes protein ATP7A.
The second domain of the human Menkes protein (MNK2), formed by 72 residues, has been expressed in Escherichia coli, and its structure has been determined by NMR in both the apo and copper-loaded forms. The structures, obtained with (13)C- and (15)N-labeled samples, are of high quality with backbone rmsd values of 0.51 and 0.41 A and CYANA target functions of 0.39 and 0.38 A(2), respectively. The loop involved in copper binding is part of a hydrophobic patch, which is maintained in both forms. Conformational mobility is observed in the apo form in the same loop. A comparison with metallochaperones and soluble domains of P-type ATPases allows us to relate the primary structure to the occurrence of structural rearrangements upon copper binding.
Banci
Lucia
L
Magnetic Resonance Center, University of Florence, Via L. Sacconi 6, 50019 Sesto Fiorentino, Italy.
Bertini
Ivano
I
Del Conte
Rebecca
R
D'Onofrio
Mariapina
M
Rosato
Antonio
A
D000251:Adenosine Triphosphatases / Q000737:chemistry*; D001059:Apoproteins / Q000737:chemistry*; D027682:Cation Transport Proteins / Q000737:chemistry*; D003300:Copper / Q000737:chemistry*; D000073840:Copper-Transporting ATPases; D005288:Ferredoxins / Q000737:chemistry; D006801:Humans; D007706:Menkes Kinky Hair Syndrome / Q000201:enzymology; D008667:Metalloproteins / Q000737:chemistry*; D018832:Molecular Chaperones / Q000737:chemistry; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D010446:Peptide Fragments / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry*; D012996:Solutions; D013816:Thermodynamics
D001059:Apoproteins; D027682:Cation Transport Proteins; D005288:Ferredoxins; D008667:Metalloproteins; D018832:Molecular Chaperones; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D012996:Solutions; D003300:Copper; D000251:Adenosine Triphosphatases; C081184:ATP7A protein, human; D000073840:Copper-Transporting ATPases