title: Solution structure of the fourth metal-binding domain from the Menkes copper-transporting ATPase.
abstract: Menkes disease is an X-linked disorder in copper transport that results in death during early childhood. The solution structures of both apo and Ag(I)-bound forms of the fourth metal-binding domain (mbd4) from the Menkes copper-transporting ATPase have been solved. The 72-residue mbd4 has a ferredoxin-like beta alpha beta beta alpha beta fold. Structural differences between the two forms are limited to the metal-binding loop, which is disordered in the apo structure but well ordered in the Ag(I)-bound structure. Ag(I) binds in a linear bicoordinate manner to the two Cys residues of the conserved GMTCxxC motif; Cu(I) likely coordinates in a similar manner. Menkes mbd4 is thus the first bicoordinate copper-binding protein to be characterized structurally. Sequence comparisons with other heavy-metal-binding domains reveal a conserved hydrophobic core and metal-binding motif.
authors.affiliation: Howard Hughes Medical Institute, University of California, San Francisco 94143, USA.
authors.forename: J
authors.initials: J
authors.lastname: Gitschier
authors.forename: B
authors.initials: B
authors.lastname: Moffat
authors.forename: D
authors.initials: D
authors.lastname: Reilly
authors.forename: W I
authors.initials: WI
authors.lastname: Wood
authors.forename: W J
authors.initials: WJ
authors.lastname: Fairbrother
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000648:ultrastructure*; D000595:Amino Acid Sequence; D001059:Apoproteins / Q000737:chemistry / Q000648:ultrastructure; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry / Q000648:ultrastructure*; D027682:Cation Transport Proteins; D003300:Copper; D000073840:Copper-Transporting ATPases; D003545:Cysteine / Q000737:chemistry; D006801:Humans; D008565:Membrane Proteins / Q000648:ultrastructure; D019216:Metals, Heavy; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012996:Solutions; D013329:Structure-Activity Relationship
chemical_list: D001059:Apoproteins; D002352:Carrier Proteins; D027682:Cation Transport Proteins; D008565:Membrane Proteins; D019216:Metals, Heavy; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D012996:Solutions; D003300:Copper; D000251:Adenosine Triphosphatases; C081184:ATP7A protein, human; D000073840:Copper-Transporting ATPases; D003545:Cysteine