Crosstalk between Cu(i) and Zn(ii) homeostasis via Atx1 and cognate domains

Badarau, Adriana; Baslé, Arnaud; Firbank, S.J.; Dennison, Christopher

doi:10.1039/c3cc42709a

Cited by 16 publications

(15 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This arrangement (contact area ∼450 Å 2 ) is remarkably similar to that of the side-to-side Cu(I) 2 –Atx1 dimer 12 (rmsd for C α atoms of ∼0.6 Å for each of the two monomers) even though the tetranuclear Cu(I) cluster is replaced by a single Zn(II) ion. This dimer is also very similar to that observed for WT Zn(II)–Atx1, 31 though some of the monomer-monomer interactions are different [oligomeric (mainly dimeric) forms are commonly observed in crystal structures of metalated forms of this Atx1 12,31 ]. The Zn(II) site in the Atx1 ZiaA N dimer is coordinated by Cys12 and Cys15 from each monomer in a tetrahedral arrangement, with Zn(II)–S γ distances of ∼2.3–2.4 Å and S γ –Zn–S γ angles of 101–121°.…”

Section: Resultssupporting

confidence: 74%

“…16 The unsaturated nature of such a Zn(II) site also makes it prone to coordinating additional ligands, such as Asp18 in ZiaA N . Two additional Cys ligands can also be recruited from a second protein molecule, as seen in the crystal structure of Zn(II)–Atx1 ZiaA N (Figure 6), and as indicated for other proteins in this work, and also WT Atx1, 14,31 by studies in solution (Figures 2 and 3, and Figures S2 and S3 and Table S3 in the Supporting Information). These tetrathiolate sites are reminiscent of Zn(II) structural sites, 7 and their buried nature suggests they have limited functionality for Zn(II) trafficking but may play a role in storing the metal.…”

Section: Resultssupporting

confidence: 72%

See 1 more Smart Citation

Investigating the Role of Zinc and Copper Binding Motifs of Trafficking Sites in the Cyanobacterium Synechocystis PCC 6803

et al. 2013

Self Cite

View full text Add to dashboard Cite

Although zinc and copper are required by proteins with very different functions, these metals can be delivered to cellular locations by homologous metal transporters within the same organism, as demonstrated by the cyanobacterial (Synechocystis PCC 6803) zinc exporter ZiaA and thylakoidal copper importer PacS. The N-terminal metal-binding domains of these transporters (ZiaAN and PacSN, respectively) have related ferredoxin folds also found in the metallochaperone Atx1, which delivers copper to PacS, but differ in the residues found in their M/IXCXXC metal-binding motifs. To investigate the role of the nonconserved residues in this region on metal binding, the sequence from ZiaAN has been introduced into Atx1 and PacSN, and the motifs of Atx1 and PacSN swapped. The motif sequence can tune Cu(I) affinity only approximately 3-fold. However, the introduction of the ZiaAN motif (MDCTSC) dramatically increases the Zn(II) affinity of both Atx1 and PacSN by up to 2 orders of magnitude. The Atx1 mutant with the ZiaAN motif crystallizes as a side-to-side homodimer very similar to that found for [Cu(I)2–Atx1]2 (Badarau20726513Biochemistry2010497798). In a crystal structure of the PacSN mutant possessing the ZiaAN motif (PacSNZiaAN), the Asp residue from the metal-binding motif coordinates Zn(II). This demonstrates that the increased Zn(II) affinity of this variant and the high Zn(II) affinity of ZiaAN are due to the ability of the carboxylate to ligate this metal ion. Comparison of the Zn(II) sites in PacSNZiaAN structures provides additional insight into Zn(II) trafficking in cyanobacteria.

show abstract

Section: Resultssupporting

confidence: 74%

Section: Resultssupporting

confidence: 72%

Investigating the Role of Zinc and Copper Binding Motifs of Trafficking Sites in the Cyanobacterium Synechocystis PCC 6803

et al. 2013

Self Cite

View full text Add to dashboard Cite

show abstract

“…As such, there is a strong implication for the presence of cytosolic zinc chaperones that can sequester metal during excess metal stress and deliver it to appropriate targets under metal starvation. Although none have been conclusively identified to date, there is evidence that members of the COG0523 (9, 10) (NiFe hydrogenase and urease maturation factor) and Atx1 (11,12) (copper metallochaperone) families may act in this capacity. In eukaryotes, metallothionein (13) and histidineproline-rich glycoprotein (14) have been implicated as possible zinc metallochaperones.…”

mentioning

confidence: 99%

AztD, a Periplasmic Zinc Metallochaperone to an ATP-binding Cassette (ABC) Transporter System in Paracoccus denitrificans

Handali¹,

Roychowdhury²,

Neupane

et al. 2015

Journal of Biological Chemistry

View full text Add to dashboard Cite

“…g . [ 35 ]). For example, a human copper chaperone HAH1 is a copper-binding HMA domain protein and forms a tight Zn 2+ -mediated complex with the HMA domain of its physiological partner ATP7a/b [ 36 ].…”

Section: Resultsmentioning

confidence: 99%

Identification of a novel zinc-binding protein, C1orf123, as an interactor with a heavy metal-associated domain

Furukawa¹,

Lim²,

Tosha³

et al. 2018

PLoS ONE

View full text Add to dashboard Cite

Heavy metal-associated (HMA) domains bind metal ions at its Cys-x-x-Cys (CxxC) motif and constitute an intracellular network for trafficking of metal ions for utilization and detoxification. We thus expect that novel metalloproteins can be identified by screening proteins interacting with a HMA domain. In this study, we performed yeast two-hybrid screening of the human proteome and found an uncharacterized protein encoded as open reading frame 123 in chromosome 1 (C1orf123) that can interact specifically with the HMA domain of a copper chaperone for superoxide dismutase (CCSdI). Our X-ray structural analysis of C1orf123 further revealed that it binds a Zn2+ ion in a tetrahedral coordination with four thiolate groups from two conserved CxxC motifs. For the interaction between C1orf123 and CCSdI, the CxxC motifs in both C1orf123 and CCSdI were required, implying metal-mediated interaction through the CxxC motifs. Notably, C1orf123 did not interact with several other HMA domains containing CxxC motifs, supporting high specificity in the interaction between C1orf123 and CCSdI. Based upon these results, we further discuss functional and structural significance of the interaction between C1orf123 and CCS.

show abstract

Crosstalk between Cu(i) and Zn(ii) homeostasis via Atx1 and cognate domains

Abstract: The copper metallochaperone Atx1 and the N-terminal metal-binding domain of a copper-transporting ATP-ase can form tight Zn(ii)-mediated hetero-complexes in both cyanobacteria and humans.

Cited by 16 publications

References 36 publications

Investigating the Role of Zinc and Copper Binding Motifs of Trafficking Sites in the Cyanobacterium Synechocystis PCC 6803

Investigating the Role of Zinc and Copper Binding Motifs of Trafficking Sites in the Cyanobacterium Synechocystis PCC 6803

AztD, a Periplasmic Zinc Metallochaperone to an ATP-binding Cassette (ABC) Transporter System in Paracoccus denitrificans

Identification of a novel zinc-binding protein, C1orf123, as an interactor with a heavy metal-associated domain

Contact Info

Product

Resources

About