Copper-binding properties of the BIR2 and BIR3 domains of the X-linked inhibitor of apoptosis protein

Liang, Yiwen; Ewing, Patrick M.; Laursen, Willem J.; Tripp, Valerie T.; Singh, Swati; Splan, Kathryn E.

doi:10.1016/j.jinorgbio.2014.07.010

Cited by 15 publications

(12 citation statements)

References 24 publications

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“…XIAP has been shown to regulate cellular copper homeostasis, and recent data suggested a direct interaction between copper and XIAP 11 , 12 . It has been hypothesized that copper binding occurs either by displacement of Zn(II) in the zinc finger, or at additional sites on the surface.…”

Section: Resultsmentioning

confidence: 99%

“…It was also suggested that XIAP binds copper via the coordination of cysteines and it undergoes conformation changes upon copper binding 11 , resulting in decreased stability of XIAP. A later study showed that several cysteine residues in the BIR2 and BIR3 domains can coordinate copper(I), both at the zinc binding site and at additional surface sites 12 . Compared with BIR2 and BIR3, BIR1 was less studied, even though it has been reported by X-ray crystallography that BIR1 forms dimeric complex either in its free state or complexed with TAB1 7 .…”

Section: Introductionmentioning

confidence: 99%

“…In human cells, the concentration of copper is tightly controlled by copper chaperones and imbalances of copper concentration results in diseases like Menkes or Wilson’s disease 9 . Recent studies have shown that XIAP is involved in cellular copper homeostasis and the direct interaction of XIAP with copper ions was reported 10 – 12 . It was also suggested that XIAP binds copper via the coordination of cysteines and it undergoes conformation changes upon copper binding 11 , resulting in decreased stability of XIAP.…”

Section: Introductionmentioning

confidence: 99%

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Solution structure and interaction with copper in vitro and in living cells of the first BIR domain of XIAP

Hou

Polykretis

Luchinat

et al. 2017

Sci Rep

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The X-chromosome linked inhibitor of apoptosis (XIAP) is a multidomain metalloprotein involved in caspase inhibition and in copper homeostasis. It contains three zinc-binding baculoviral IAP repeats (BIR) domains, which are responsible for caspase interaction. Recently, it has been suggested that the BIR domains can bind copper, however high resolution data on such interaction is missing. Here we characterize by NMR the structural properties of BIR1 in solution, and the effects of its interaction with copper both in vitro and in physiological environments. BIR1 is dimeric in solution, consistent with the X-ray structure. Cysteine 12, located in the unfolded N-terminal region, has a remarkably low redox potential, and is prone to oxidation even in reducing physiological environments. Interaction of BIR1 with copper(II) results in the oxidation of cysteine 12, with the formation of either an intermolecular disulfide bond between two BIR1 molecules or a mixed disulfide bond with glutathione, whereas the zinc binding site is not affected by the interaction.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Solution structure and interaction with copper in vitro and in living cells of the first BIR domain of XIAP

Hou

Polykretis

Luchinat

et al. 2017

Sci Rep

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show abstract

“…Two potential mechanisms could lead to the copper-dependent increase of electrophoretic mobility. Because of the multiple metal binding motifs in the XIAP protein 40 reports have shown that the BIR domains of XIAP contain multiple cysteine residues that are susceptible to copper-regulated oxidation 41,39 , which could also account for the change in electrophoretic mobility. Although the nature of copper-induced XIAP shift remains unclear, we found that recombinant XIAP expressed in the presence of copper exhibited enhanced E3-ligase activity, indicating that copper can functionally impact XIAP.…”

Section: Discussionmentioning

confidence: 99%

“…XIAP also catalyzes the transfer of K48-linked ubiquitin moieties to caspase 3 to mediate its proteasome-dependent degradation 36,37 . Interestingly, a multitude of evidence suggests that the conformation of XIAP can be regulated by copper: supplementation to recombinant XIAP, that addition of copper to cell cultures induces a characteristic shift in XIAP mobility on nondenaturing gel 38 , that addition of cuprous cations to recombinant XIAP protein leads to the formation of oligomers 39 , and that copper can rescue zinc depletion-induced degradation of XIAP 40 . Furthermore, NMR analysis indicates that certain cysteine residues in XIAP are susceptible to copper-mediated oxidation, thereby regulating the oligomerization state of the protein 41 .…”

Section: Steap4 Sustains Nf-κb Activation and Inhibits Apoptosismentioning

confidence: 99%

Inflammation mobilizes copper metabolism to promote colon tumorigenesis via an IL-17-STEAP4-XIAP axis

et al. 2020

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Copper levels are known to be elevated in inflamed and malignant tissues. But the mechanism underlying this selective enrichment has been elusive. In this study, we report a axis by which inflammatory cytokines, such as IL-17, drive cellular copper uptake via the induction of a metalloreductase, STEAP4. IL-17-induced elevated intracellular copper level leads to the activation of an E3-ligase, XIAP, which potentiates IL-17-induced NFκB activation and suppresses the caspase 3 activity. Importantly, this IL-17-induced STEAP4-dependent cellular copper uptake is critical for colon tumor formation in a murine model of colitis-associated tumorigenesis and STEAP4 expression correlates with IL-17 level and XIAP activation in human colon cancer. In summary, this study reveals a IL-17-STEAP4-XIAP axis through which the inflammatory response induces copper uptake, promoting colon tumorigenesis.

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APEX2‐based Proximity Labeling of Atox1 Identifies CRIP2 as a Nuclear Copper‐binding Protein that Regulates Autophagy Activation

Chen

Zhang

et al. 2021

Angewandte Chemie

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Mammalian cell nuclei contain copper,a nd cancer cells are knownt oa ccumulate aberrantly high copper levels, yet the mechanisms underlying nuclear accumulation and coppersbroader functional significance remain poorly understood. Here,b yc ombining APEX2-based proximity labeling focused on the copper chaperone Atox1 with mass spectrometry we identified ap reviously unrecognized nuclear copper binding protein, Cysteine-rich protein 2(CRIP2), that interacts with Atox1 in the nucleus.Weshowthat Atox1 transfers copper to CRIP2, whichi nduces ac hange in CRIP2'ss econdary structure that ultimately promotes its ubiquitin-mediated proteasomal degradation. Finally,w ed emonstrate that depletion of CRIP2-as well as copper-induced CRIP2 degradationelevates ROSl evels and activates autophagy in H1299 cells. Thus,o ur study establishes that CRIP2 as an autophagic suppressor protein and implicates CRIP2-mediated copper metabolism in the activation of autophagy in cancer cells.

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Copper-binding properties of the BIR2 and BIR3 domains of the X-linked inhibitor of apoptosis protein

Cited by 15 publications

References 24 publications

Solution structure and interaction with copper in vitro and in living cells of the first BIR domain of XIAP

Solution structure and interaction with copper in vitro and in living cells of the first BIR domain of XIAP

Inflammation mobilizes copper metabolism to promote colon tumorigenesis via an IL-17-STEAP4-XIAP axis

APEX2‐based Proximity Labeling of Atox1 Identifies CRIP2 as a Nuclear Copper‐binding Protein that Regulates Autophagy Activation

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