4BTE

DJ-1 Cu(I) complex

Summary for 4BTE

• Entry DOI: 10.2210/pdb4bte/pdb
• Descriptor: PROTEIN DJ-1, COPPER (I) ION (3 entities in total)
• Functional Keywords: hydrolase, copper chaperone, parkinson's disease, superoxide dismutase activation, multi-functional
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cytoplasm: Q99497
• Total number of polymer chains: 1
• Total formula weight: 19980.60

Authors

Puno, M.R.A.,Odell, M.,Moody, P.C.E. (deposition date: 2013-06-14, release date: 2013-11-06, Last modification date: 2023-12-20)

Primary citation

Puno, M.R.,Patel, N.A.,Moller, S.G.,Robinson, C.V.,Moody, P.C.E.,Odell, M.
Structure of Cu(I)-Bound Dj-1 Reveals a Biscysteinate Metal Binding Site at the Homodimer Interface: Insights Into Mutational Inactivation of Dj-1 in Parkinsonism.
J.Am.Chem.Soc., 135:15974-, 2013

PubMed 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 × 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.

PubMed: 24144264
DOI: 10.1021/JA406010M

Experimental method

X-RAY DIFFRACTION (1.38 Å)