The Crystal Structure of DJ-1, a Protein Related to Male Fertility and Parkinson's Disease

• Published in: The Journal of biological chemistry 2003-08, Vol.278 (33), p.31380-31384
• Main Authors: Honbou, Kazuya, Suzuki, Nobuo N., Horiuchi, Masataka, Niki, Takeshi, Taira, Takahiro, Ariga, Hiroyoshi, Inagaki, Fuyuhiko
• Format: Article
• Language: English
• Subjects: Cloning, Molecular; Crystallography, X-Ray; Dimerization; Fertility - physiology; Humans; Infertility, Male - genetics; Intracellular Signaling Peptides and Proteins; Male; Oncogene Proteins - chemistry; Oncogene Proteins - genetics; Oncogene Proteins - metabolism; Oxidative Stress - physiology; Parkinson Disease - genetics; Protein Deglycase DJ-1; Protein Structure, Secondary; Protein Structure, Tertiary; Structure-Activity Relationship
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M305878200

DJ-1 is a multifunctional protein that plays essential roles in tissues with higher order biological functions such as the testis and brain. DJ-1 is related to male fertility, and its level in sperm decreases in response to exposure to sperm toxicants. DJ-1 has also been identified as a hydroperoxide-responsive protein. Recently, a mutation of DJ-1 was found to be responsible for familial Parkinson's disease. Here, we present the crystal structure of DJ-1 refined to 1.95-Å resolution. DJ-1 forms a dimer in the crystal, and the monomer takes a flavodoxin-like Rossmann-fold. DJ-1 is structurally most similar to the monomer subunit of protease I, the intracellular cysteine protease from Pyrococcus horikoshii, and belongs to the Class I glutamine amidotransferase-like superfamily. However, DJ-1 contains an additional α-helix at the C-terminal region, which blocks the putative catalytic site of DJ-1 and appears to regulate the enzymatic activity. DJ-1 may induce conformational changes to acquire catalytic activity in response to oxidative stress.