The crystal structure of DJ-1, a protein related to male fertility and Parkinson's disease.
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-A 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 alpha-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.
Honbou
Kazuya
K
Department of Structural Biology, Graduate School of Pharmaceutical Sciences, Hokkaido University, N-12, W-6, Kita-ku, Sapporo, 060-0812, Japan.
Suzuki
Nobuo N
NN
Horiuchi
Masataka
M
Niki
Takeshi
T
Taira
Takahiro
T
Ariga
Hiroyoshi
H
Inagaki
Fuyuhiko
F
D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D019281:Dimerization; D005298:Fertility / Q000502:physiology; D006801:Humans; D007248:Infertility, Male / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D015513:Oncogene Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D010300:Parkinson Disease / Q000235:genetics*; D000071617:Protein Deglycase DJ-1; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1