Thermodynamic and structural characterization of the specific binding of Zn(II) to human protein DJ-1.
Mutations of DJ-1 cause familial Parkinson's disease (PD), although the role of DJ-1 in PD remains unresolved. Very recent reports have shown that DJ-1 interacts with copper ions. This evidence opens new avenues to understanding the function of DJ-1 and its role in PD. Herein, we report that Zn(II) binds to DJ-1 with great selectivity among the other metals examined: Mn(II), Fe(II), Co(II), Ni(II), and Cu(II). High-resolution X-ray crystallography (1.18 Å resolution) shows Zn(II) is coordinated to the protein by the key residues Cys106 and Glu18. These results suggest that DJ-1 may be regulated and/or stabilized by Zn(II).
Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo , Kashiwa 277-8562, Japan.
Shinya
S
Tashiro
Jose M M
JM
Caaveiro
Chun-Xiang
CX
Wu
Quyen Q
QQ
Hoang
Kouhei
K
Tsumoto
D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D015513:Oncogene Proteins / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D000071617:Protein Deglycase DJ-1; D013816:Thermodynamics; D015032:Zinc / Q000378:metabolism*
D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1; D015032:Zinc