2ew9

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Solution structure of apoWLN5-6

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

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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