2ew9 is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
[ATP7B_HUMAN] Involved in the export of copper out of the cells, such as the efflux of hepatic copper into the bile.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Human Wilson protein is a copper-transporting ATPase located in the secretory pathway possessing six N-terminal metal-binding domains. Here we focus on the function of the metal-binding domains closest to the vesicular portion of the copper pump, i.e., domain 4 (WLN4), and a construct of domains 5 and 6 (WLN5-6). For comparison purposes, some experiments were also performed with domain 2 (WLN2). The solution structure of apoWLN5-6 consists of two ferredoxin folds connected by a short linker, and (15)N relaxation rate measurements show that it behaves as a unit in solution. An NMR titration of apoWLN5-6 with the metallochaperone Cu(I)HAH1 reveals no complex formation and no copper exchange between the two proteins, whereas titration of Cu(I)HAH1 with WLN4 shows the formation of an adduct that is in fast exchange on the NMR time scale with the isolated protein species as confirmed by (15)N relaxation data. A similar interaction is also observed between Cu(I)HAH1 and WLN2; however, the relative amount of the adduct in the protein mixture is lower. An NMR titration of apoWLN5-6 with Cu(I)WLN4 shows copper transfer, first to WLN6 then to WLN5, without the formation of an adduct. Therefore, we suggest that WLN4 and WLN2 are two acceptors of Cu(I) from HAH1, which then somehow route copper to WLN5-6, before the ATP-driven transport of copper across the vesicular membrane.
Structure of human Wilson protein domains 5 and 6 and their interplay with domain 4 and the copper chaperone HAH1 in copper uptake.,Achila D, Banci L, Bertini I, Bunce J, Ciofi-Baffoni S, Huffman DL Proc Natl Acad Sci U S A. 2006 Apr 11;103(15):5729-34. Epub 2006 Mar 29. PMID:16571664[52]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
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↑Butler P, McIntyre N, Mistry PK. Molecular diagnosis of Wilson disease. Mol Genet Metab. 2001 Mar;72(3):223-30. PMID:11243728 doi:10.1006/mgme.2000.3143
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↑Todorov T, Savov A, Jelev H, Panteleeva E, Konstantinova D, Krustev Z, Mihaylova V, Tournev I, Tankova L, Tzolova N, Kremensky I. Spectrum of mutations in the Wilson disease gene (ATP7B) in the Bulgarian population. Clin Genet. 2005 Nov;68(5):474-6. PMID:16207219 doi:10.1111/j.1399-0004.2005.00516.x
↑Gromadzka G, Schmidt HH, Genschel J, Bochow B, Rodo M, Tarnacka B, Litwin T, Chabik G, Czlonkowska A. Frameshift and nonsense mutations in the gene for ATPase7B are associated with severe impairment of copper metabolism and with an early clinical manifestation of Wilson's disease. Clin Genet. 2005 Dec;68(6):524-32. PMID:16283883 doi:10.1111/j.1399-0004.2005.00528.x
↑Cox DW, Prat L, Walshe JM, Heathcote J, Gaffney D. Twenty-four novel mutations in Wilson disease patients of predominantly European ancestry. Hum Mutat. 2005 Sep;26(3):280. PMID:16088907 doi:10.1002/humu.9358
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↑Davies LP, Macintyre G, Cox DW. New mutations in the Wilson disease gene, ATP7B: implications for molecular testing. Genet Test. 2008 Mar;12(1):139-45. doi: 10.1089/gte.2007.0072. PMID:18373411 doi:10.1089/gte.2007.0072
↑Hsi G, Cullen LM, Macintyre G, Chen MM, Glerum DM, Cox DW. Sequence variation in the ATP-binding domain of the Wilson disease transporter, ATP7B, affects copper transport in a yeast model system. Hum Mutat. 2008 Apr;29(4):491-501. doi: 10.1002/humu.20674. PMID:18203200 doi:10.1002/humu.20674
↑Abdel Ghaffar TY, Elsayed SM, Elnaghy S, Shadeed A, Elsobky ES, Schmidt H. Phenotypic and genetic characterization of a cohort of pediatric Wilson disease patients. BMC Pediatr. 2011 Jun 17;11:56. doi: 10.1186/1471-2431-11-56. PMID:21682854 doi:10.1186/1471-2431-11-56
↑Achila D, Banci L, Bertini I, Bunce J, Ciofi-Baffoni S, Huffman DL. Structure of human Wilson protein domains 5 and 6 and their interplay with domain 4 and the copper chaperone HAH1 in copper uptake. Proc Natl Acad Sci U S A. 2006 Apr 11;103(15):5729-34. Epub 2006 Mar 29. PMID:16571664
