Copper transfer studies between the N-terminal copper binding domains one and four of human Wilson protein

2006 ◽  
Vol 1760 (6) ◽  
pp. 907-912 ◽  
Author(s):  
Jennifer Bunce ◽  
David Achila ◽  
Evan Hetrick ◽  
Leighann Lesley ◽  
David L. Huffman
Keyword(s):  
Copper Binding ◽  
Binding Domains ◽  
Wilson Protein ◽  
Copper Transfer

scholarly journals Redox-regulated dynamic interplay between Cox19 and the copper-binding protein Cox11 in the intermembrane space of mitochondria facilitates biogenesis of cytochrome c oxidase

2015 ◽  
Vol 26 (13) ◽  
pp. 2385-2401 ◽  
Author(s):  
Manuela Bode ◽  
Michael W. Woellhaf ◽  
Maria Bohnert ◽  
Martin van der Laan ◽  
Frederik Sommer ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Specific Binding ◽  
Hydrophobic Surface ◽  
Cysteine Residue ◽  
Oxidative Modification ◽  
Intermembrane Space ◽  
Copper Binding ◽  
C Protein ◽  
Copper Transfer

Members of the twin Cx9C protein family constitute the largest group of proteins in the intermembrane space (IMS) of mitochondria. Despite their conserved nature and their essential role in the biogenesis of the respiratory chain, the molecular function of twin Cx9C proteins is largely unknown. We performed a SILAC-based quantitative proteomic analysis to identify interaction partners of the conserved twin Cx9C protein Cox19. We found that Cox19 interacts in a dynamic manner with Cox11, a copper transfer protein that facilitates metalation of the Cu(B) center of subunit 1 of cytochrome c oxidase. The interaction with Cox11 is critical for the stable accumulation of Cox19 in mitochondria. Cox19 consists of a helical hairpin structure that forms a hydrophobic surface characterized by two highly conserved tyrosine-leucine dipeptides. These residues are essential for Cox19 function and its specific binding to a cysteine-containing sequence in Cox11. Our observations suggest that an oxidative modification of this cysteine residue of Cox11 stimulates Cox19 binding, pointing to a redox-regulated interplay of Cox19 and Cox11 that is critical for copper transfer in the IMS and thus for biogenesis of cytochrome c oxidase.

Characterization of the Menkes Protein Copper-Binding Domains and Their Role in Copper-Induced Protein Relocalization

1999 ◽  
Vol 8 (8) ◽  
pp. 1473-1478 ◽  
Author(s):  
I. D. Goodyer ◽  
E. E. Jones ◽  
A. P. Monaco ◽  
M. J. Francis
Keyword(s):  
Copper Binding ◽  
Binding Domains ◽  
Menkes Protein

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.

NMR Characterization of Copper-Binding Domains 4−6 of ATP7B,

Biochemistry ◽  
2010 ◽  
Vol 49 (39) ◽  
pp. 8468-8477 ◽  
Author(s):  
Negah Fatemi ◽  
Dmitry M. Korzhnev ◽  
Algirdas Velyvis ◽  
Bibudhendra Sarkar ◽  
Julie D. Forman-Kay
Keyword(s):  
Copper Binding ◽  
Binding Domains ◽  
Nmr Characterization

scholarly journals Improvement of laccase activity by silencing PacC in Ganoderma lucidum

2021 ◽  
Author(s):  
Mingwen Zhao ◽  
Jing Zhu ◽  
Shuqi Song ◽  
Lindan Lian ◽  
Liang Shi ◽  
...  
Keyword(s):  
Ganoderma Lucidum ◽  
Laccase Activity ◽  
Ph Value ◽  
Fold Increase ◽  
White Rot ◽  
White Rot Fungus ◽  
Copper Binding ◽  
Multicopper Oxidases ◽  
Binding Domains ◽  
Laccase Genes

Abstract Ganoderma lucidum is a representative white-rot fungus that has great potential to degrade lignocellulose biomass. Laccase is recognized as a class of the most important lignin-degrading enzymes in G. lucidum. However, the comprehensive regulatory mechanisms of laccase are still lacking. Based on the genome sequence of G. lucidum, 15 laccase genes were identified and their encoding proteins were analyzed in this study. All of the laccase proteins are predicted to be multicopper oxidases with conserved copper-binding domains. Most laccase proteins were secreted enzymes in addition to Lac14 in which the signal peptide could not be predicted. The activity of all laccases showed the highest level at pH 3.0 or pH 7.0, with total laccase activity of approximately 200 U/mg protein. Silencing PacC resulted in a 5.2 fold increase in laccase activity compared with WT. Five laccase genes (lac1, lac6, lac9, lac10 and lac14) showed an increased transcription levels (approximately 1.5-5.6 fold) in the PacC-silenced strains versus that in WT, while other laccase genes were downregulated or unchanged. The extracellular pH value was about 3.1, which was more acidic in the PacC-silenced strains than in the WT (pH 3.5). Moreover, maintaining the fermentation pH resulted in a downregulation of laccase activity which is induced by silencing PacC Our findings indicate that in addition to its function in acidification of environmental pH, PacC plays an important role in regulating laccase activity in fungi.

scholarly journals Structural basis and mechanism for metallochaperone-assisted assembly of the CuA center in cytochrome oxidase

2019 ◽  
Vol 5 (7) ◽  
pp. eaaw8478 ◽  
Author(s):  
Fabia Canonica ◽  
Daniel Klose ◽  
Raphael Ledermann ◽  
Maximilian M. Sauer ◽  
Helge K. Abicht ◽  
...  
Keyword(s):  
Binding Sites ◽  
Structural Data ◽  
Structural Basis ◽  
Copper Binding ◽  
Redox Center ◽  
Cytochrome Oxidases ◽  
Cu Ions ◽  
Copper Transfer

The mechanisms underlying the biogenesis of the structurally unique, binuclear Cu1.5+•Cu1.5+ redox center (CuA) on subunit II (CoxB) of cytochrome oxidases have been a long-standing mystery. Here, we reconstituted the CoxB•CuA center in vitro from apo-CoxB and the holo-forms of the copper transfer chaperones ScoI and PcuC. A previously unknown, highly stable ScoI•Cu2+•CoxB complex was shown to be rapidly formed as the first intermediate in the pathway. Moreover, our structural data revealed that PcuC has two copper-binding sites, one each for Cu1+ and Cu2+, and that only PcuC•Cu1+•Cu2+ can release CoxB•Cu2+ from the ScoI•Cu2+•CoxB complex. The CoxB•CuA center was then formed quantitatively by transfer of Cu1+ from a second equivalent of PcuC•Cu1+•Cu2+ to CoxB•Cu2+. This metalation pathway is consistent with all available in vivo data and identifies the sources of the Cu ions required for CuA center formation and the order of their delivery to CoxB.

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.

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