Crystal structure of DJ-1/RS and implication on familial Parkinson's disease.
DJ-1 is a protein involved in multiple physiological processes, including cancer, Parkinson's disease, and male fertility. It is unknown how DJ-1 functions in the apparently different systems. The crystal structure of DJ-1 at 1.6 A resolution shows that DJ-1 is a helix-strand-helix sandwich and forms a dimer. The DJ-1 structure is similar to the members of the intracellular protease PfpI family. However, the catalytic triad of Cys-His-Glu is not strictly conserved in DJ-1, implying that DJ-1 has a different catalytic mechanism if it acts as a protease or DJ-1 serves as a regulatory protein in the physiological processes. The structure shows that Leu166 positions in the middle of a helix and thus predicts that the L166P mutation will bend the helix and impact the dimerization of DJ-1. As a result, the conformational changes may diminish the DJ-1 binding with its partner, leading to the familial Parkinson's disease caused by the single L166P mutation.
Huai
Qing
Q
Department of Biochemistry and Biophysics and Lineberger Comprehensive Cancer Center, The University of North Carolina, Chapel Hill, NC 27599-7260, USA.
Sun
Yingjie
Y
Wang
Huanchen
H
Chin
Lih Shen
LS
Li
Lian
L
Robinson
Howard
H
Ke
Hengming
H
D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D019281:Dimerization; D005192:Family Health; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008869:Microtubule-Associated Proteins / Q000737:chemistry* / Q000235:genetics; D015513:Oncogene Proteins / Q000737:chemistry* / Q000235:genetics; D010300:Parkinson Disease / Q000209:etiology*; D017354:Point Mutation; D011487:Protein Conformation; D000071617:Protein Deglycase DJ-1; D017433:Protein Structure, Secondary
D047908:Intracellular Signaling Peptides and Proteins; D008869:Microtubule-Associated Proteins; D015513:Oncogene Proteins; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1