Crystal Structure of the Human Copper Chaperone ATOX1 Bound to Zinc Ion

The bioavailability of copper (Cu) in human cells may depend on a complex interplay with zinc (Zn) ions. We investigated the ability of the Zn ion to target the human Cu-chaperone Atox1, a small cytosolic protein capable of anchoring Cu(I), by a conserved surface-exposed Cys-X-X-Cys (CXXC) motif, an...

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Bibliographic Details
Published in:Biomolecules (Basel, Switzerland) Switzerland), 2022-10, Vol.12 (10), p.1494
Main Authors: Mangini, Vincenzo, Belviso, Benny Danilo, Nardella, Maria Incoronata, Natile, Giovanni, Arnesano, Fabio, Caliandro, Rocco
Format: Article
Language:English
Subjects:
Bioavailability
Cell physiology
Chelating agents
Copper
copper transport proteins
Crystal structure
Crystallization
Crystals
Disease
Enzymes
Golgi apparatus
Homeostasis
Metabolism
Metal ions
Metallochaperones
molecular structure
Physiological aspects
Proteins
Structure
X-ray crystallography
X-ray diffraction
Zinc
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Summary:The bioavailability of copper (Cu) in human cells may depend on a complex interplay with zinc (Zn) ions. We investigated the ability of the Zn ion to target the human Cu-chaperone Atox1, a small cytosolic protein capable of anchoring Cu(I), by a conserved surface-exposed Cys-X-X-Cys (CXXC) motif, and deliver it to Cu-transporting ATPases in the trans-Golgi network. The crystal structure of Atox1 loaded with Zn displays the metal ion bridging the CXXC motifs of two Atox1 molecules in a homodimer. The identity and location of the Zn ion were confirmed through the anomalous scattering of the metal by collecting X-ray diffraction data near the Zn K-edge. Furthermore, soaking experiments of the Zn-loaded Atox1 crystals with a strong chelating agent, such as EDTA, caused only limited removal of the metal ion from the tetrahedral coordination cage, suggesting a potential role of Atox1 in Zn metabolism and, more generally, that Cu and Zn transport mechanisms could be interlocked in human cells.
ISSN:2218-273X
2218-273X
DOI:10.3390/biom12101494