4BTE: Dj-1 Cu(i) Complex

Citation:
Abstract
The Parkinsonism-associated protein DJ-1 has been suggested to activate the Cu-Zn superoxide dismutase (SOD1) by providing its copper cofactor. The structural and chemical means by which DJ-1 could support this function is unknown. In this study, we characterize the molecular interaction of DJ-1 with Cu(I). Mass spectrometric analysis indicates binding of one Cu(I) ion per DJ-1 homodimer. The crystal structure of DJ-1 bound to Cu(I) confirms metal coordination through a docking accessible biscysteinate site formed by juxtaposed cysteine residues at the homodimer interface. Spectroscopy in crystallo validates the identity and oxidation state of the bound metal. The measured subfemtomolar dissociation constant (Kd = 6.41 x 10-16 M) of DJ-1 for Cu(I) supports the physiological retention of the metal ion. Our results highlight the requirement of a stable homodimer for copper binding by DJ-1. Parkinsonism-linked mutations that weaken homodimer interactions will compromise this capability.
PDB ID: 4BTEDownload
MMDB ID: 114836
PDB Deposition Date: 2013/6/14
Updated in MMDB: 2013/12
Experimental Method:
x-ray diffraction
Resolution: 1.38  Å
Source Organism:
Similar Structures:
Biological Unit for 4BTE: dimeric; determined by software (PISA)
Molecular Components in 4BTE
Label Count Molecule
Proteins (2 molecules)
2
Protein Dj-1(Gene symbol: PARK7)
Molecule annotation
Chemical (1 molecule)
1
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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