scholarly journals Disease-causing point-mutations in metal-binding domains of Wilson disease protein decrease stability and increase structural dynamics

BioMetals ◽  
2016 ◽  
Vol 30 (1) ◽  
pp. 27-35 ◽  
Author(s):  
Ranjeet Kumar ◽  
Candan Ariöz ◽  
Yaozong Li ◽  
Niklas Bosaeus ◽  
Sandra Rocha ◽  
...  
Keyword(s):  
Structural Dynamics ◽  
Metal Binding ◽  
Wilson Disease ◽  
Point Mutations ◽  
Binding Domains ◽  
Wilson Disease Protein ◽  
Disease Protein

scholarly journals Copper relay path through the N-terminus of Wilson disease protein, ATP7B

Metallomics ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1472-1480 ◽  
Author(s):  
Kumaravel Ponnandai Shanmugavel ◽  
Pernilla Wittung-Stafshede
Keyword(s):  
Metal Binding ◽  
Wilson Disease ◽  
Copper Transport ◽  
Binding Domains ◽  
Wilson Disease Protein ◽  
N Terminus ◽  
Disease Protein ◽  
Yeast Assay

Using a yeast assay, we identified the roles of ATP7B's six metal-binding domains in internal copper transport and soluble chaperone capacity.

Conformational Dynamics of Metal-Binding Domains in Wilson Disease Protein: Molecular Insights into Selective Copper Transfer†

Biochemistry ◽  
2009 ◽  
Vol 48 (25) ◽  
pp. 5849-5863 ◽  
Author(s):  
Agustina Rodriguez-Granillo ◽  
Alejandro Crespo ◽  
Pernilla Wittung-Stafshede
Keyword(s):  
Metal Binding ◽  
Wilson Disease ◽  
Conformational Dynamics ◽  
Binding Domains ◽  
Wilson Disease Protein ◽  
Disease Protein ◽  
Copper Transfer

scholarly journals Metal Binding Domains 3 and 4 of the Wilson Disease Protein: Solution Structure and Interaction with the Copper(I) Chaperone HAH1†‡

Biochemistry ◽  
2008 ◽  
Vol 47 (28) ◽  
pp. 7423-7429 ◽  
Author(s):  
Lucia Banci ◽  
Ivano Bertini ◽  
Francesca Cantini ◽  
Amy C. Rosenzweig ◽  
Liliya A. Yatsunyk
Keyword(s):  
Metal Binding ◽  
Wilson Disease ◽  
Solution Structure ◽  
Protein Solution ◽  
Binding Domains ◽  
Wilson Disease Protein ◽  
Disease Protein

Interdomain Interactions Modulate Collective Dynamics of the Metal-Binding Domains in the Wilson Disease Protein

2010 ◽  
Vol 114 (5) ◽  
pp. 1836-1848 ◽  
Author(s):  
Agustina Rodriguez-Granillo ◽  
Alejandro Crespo ◽  
Pernilla Wittung-Stafshede
Keyword(s):  
Metal Binding ◽  
Wilson Disease ◽  
Collective Dynamics ◽  
Binding Domains ◽  
Wilson Disease Protein ◽  
Disease Protein ◽  
Interdomain Interactions

Small pH and Salt Variations Radically Alter the Thermal Stability of Metal-Binding Domains in the Copper Transporter, Wilson Disease Protein

2013 ◽  
Vol 117 (42) ◽  
pp. 13038-13050 ◽  
Author(s):  
Lina Nilsson ◽  
Jörgen Ådén ◽  
Moritz S. Niemiec ◽  
Kwangho Nam ◽  
Pernilla Wittung-Stafshede
Keyword(s):  
Thermal Stability ◽  
Metal Binding ◽  
Wilson Disease ◽  
Copper Transporter ◽  
Binding Domains ◽  
Wilson Disease Protein ◽  
Disease Protein ◽  
Thermal Stability Of

scholarly journals Probing functional roles of Wilson disease protein (ATP7B) copper-binding domains in yeast

Metallomics ◽  
2017 ◽  
Vol 9 (7) ◽  
pp. 981-988 ◽  
Author(s):  
Kumaravel Ponnandai Shanmugavel ◽  
Dina Petranovic ◽  
Pernilla Wittung-Stafshede
Keyword(s):  
Wilson Disease ◽  
Copper Binding ◽  
Functional Roles ◽  
Binding Domains ◽  
Wilson Disease Protein ◽  
Disease Protein

A double deleted yeast system was developed to probe activity of human ATP7B variants in the presence of human Atox1.

Copper-Transfer Mechanism from the Human Chaperone Atox1 to a Metal-Binding Domain of Wilson Disease Protein

2010 ◽  
Vol 114 (10) ◽  
pp. 3698-3706 ◽  
Author(s):  
Agustina Rodriguez-Granillo ◽  
Alejandro Crespo ◽  
Dario A. Estrin ◽  
Pernilla Wittung-Stafshede
Keyword(s):  
Metal Binding ◽  
Wilson Disease ◽  
Binding Domain ◽  
Transfer Mechanism ◽  
Wilson Disease Protein ◽  
Metal Binding Domain ◽  
Disease Protein ◽  
Copper Transfer

scholarly journals Wilson disease missense mutations in ATP7B affect metal-binding domain structural dynamics

BioMetals ◽  
2019 ◽  
Vol 32 (6) ◽  
pp. 875-885 ◽  
Author(s):  
Kumaravel Ponnandai Shanmugavel ◽  
Ranjeet Kumar ◽  
Yaozong Li ◽  
Pernilla Wittung-Stafshede
Keyword(s):  
Structural Dynamics ◽  
Metal Binding ◽  
Wilson Disease ◽  
Copper Transport ◽  
Missense Mutations ◽  
Copper Binding ◽  
Structural Dynamic ◽  
Binding Domains ◽  
Metal Binding Domain ◽  
Dynamics Simulations

Abstract Wilson disease (WD) is caused by mutations in the gene for ATP7B, a copper transport protein that regulates copper levels in cells. A large number of missense mutations have been reported to cause WD but genotype–phenotype correlations are not yet established. Since genetic screening for WD may become reality in the future, it is important to know how individual mutations affect ATP7B function, with the ultimate goal to predict pathophysiology of the disease. To begin to assess mechanisms of dysfunction, we investigated four proposed WD-causing missense mutations in metal-binding domains 5 and 6 of ATP7B. Three of the four variants showed reduced ATP7B copper transport ability in a traditional yeast assay. To probe mutation-induced structural dynamic effects at the atomic level, molecular dynamics simulations (1.5 μs simulation time for each variant) were employed. Upon comparing individual metal-binding domains with and without mutations, we identified distinct differences in structural dynamics via root-mean square fluctuation and secondary structure content analyses. Most mutations introduced distant effects resulting in increased dynamics in the copper-binding loop. Taken together, mutation-induced long-range alterations in structural dynamics provide a rationale for reduced copper transport ability.

Localization of the Wilson disease protein in murine intestine

2008 ◽  
Vol 46 (09) ◽  
Author(s):  
KH Weiss ◽  
D Gotthardt ◽  
J Wurz ◽  
U Merle ◽  
W Stremmel ◽  
...  
Keyword(s):  
Wilson Disease ◽  
Wilson Disease Protein ◽  
Disease Protein
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