2ew9
From Proteopedia
(New page: 200px<br /> <applet load="2ew9" size="450" color="white" frame="true" align="right" spinBox="true" caption="2ew9" /> '''Solution structure of apoWLN5-6'''<br /> =...) |
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| - | [[Image:2ew9.gif|left|200px]]<br /> | + | [[Image:2ew9.gif|left|200px]]<br /><applet load="2ew9" size="350" color="white" frame="true" align="right" spinBox="true" |
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'''Solution structure of apoWLN5-6'''<br /> | '''Solution structure of apoWLN5-6'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Human Wilson protein is a copper-transporting ATPase located in the | + | 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. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2EW9 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Copper-exporting_ATPase Copper-exporting ATPase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.3.4 3.6.3.4] Full crystallographic information is available from [http:// | + | 2EW9 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Copper-exporting_ATPase Copper-exporting ATPase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.3.4 3.6.3.4] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2EW9 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Ciofi-Baffoni, S.]] | [[Category: Ciofi-Baffoni, S.]] | ||
| - | [[Category: SPINE, Structural | + | [[Category: SPINE, Structural Proteomics in Europe.]] |
[[Category: copper trafficking]] | [[Category: copper trafficking]] | ||
[[Category: ferrodoxin-like fold]] | [[Category: ferrodoxin-like fold]] | ||
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[[Category: structural proteomics in europe]] | [[Category: structural proteomics in europe]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:15:11 2008'' |
Revision as of 15:15, 21 February 2008
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Solution structure of apoWLN5-6
Contents |
Overview
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.
Disease
Known diseases associated with this structure: Wilson disease OMIM:[606882]
About this Structure
2EW9 is a Single protein structure of sequence from Homo sapiens. Active as Copper-exporting ATPase, with EC number 3.6.3.4 Full crystallographic information is available from OCA.
Reference
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
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