Document Detail

Lysine-60 in copper chaperone Atox1 plays an essential role in adduct formation with a target Wilson disease domain.
MedLine Citation:
PMID:  19863064     Owner:  NLM     Status:  MEDLINE    
The mechanism by which the human copper (Cu) chaperone Atox1 delivers Cu to metal-binding domains of Wilson disease (WD) protein for insertion into cuproenzymes is unclear. Using near-UV circular dichroism as a new tool to probe chaperone-target interactions, in combination with gel filtration and molecular dynamics simulations, we here demonstrate that Atox1 forms a stable Cu-dependent adduct with the fourth metal-binding domain of WD (WD4). Using point-mutated Atox1 variants, we show that the adduct forms in the absence of conserved residues M10 or T11 but K60 is essential for heterocomplex formation and Cu transfer. Dissection of heterocomplex energetic components reveals a crucial role for K60-mediated electrostatic interaction.
Faiza Hussain; Agustina Rodriguez-Granillo; Pernilla Wittung-Stafshede
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Journal of the American Chemical Society     Volume:  131     ISSN:  1520-5126     ISO Abbreviation:  J. Am. Chem. Soc.     Publication Date:  2009 Nov 
Date Detail:
Created Date:  2009-11-11     Completed Date:  2010-02-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7503056     Medline TA:  J Am Chem Soc     Country:  United States    
Other Details:
Languages:  eng     Pagination:  16371-3     Citation Subset:  IM    
Department of Biochemistry and Cell Biology, Rice University, 6100 Main Street, Houston, Texas 77251, USA.
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MeSH Terms
Adenosine Triphosphatases / chemistry*
Cation Transport Proteins / chemistry*
Computer Simulation
Copper / chemistry*
Lysine / chemistry*
Models, Chemical
Models, Molecular
Molecular Chaperones / chemistry*
Protein Conformation
Reg. No./Substance:
0/ATOX1 protein, human; 0/Cation Transport Proteins; 0/Molecular Chaperones; 56-87-1/Lysine; 7440-50-8/Copper; EC 3.6.1.-/Adenosine Triphosphatases; EC disease protein

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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