The crystal structure of DJ-1, a protein related to male fertility and bParkinson's disease
The crystal structure of DJ-1, a protein related to male fertility and bParkinson's disease
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DOI：
10.1074/jbc.m305878200
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发表时间：
2003-08-15
影响因子：
4.8
通讯作者：
Inagaki, F
中科院分区：
文献类型：
--
作者：
Honbou, K;Suzuki, NN;Inagaki, F
DJ-1是一种多功能蛋白质，在睾丸、脑等具有较高生物功能的组织中发挥重要作用。DJ-1与男性生育能力有关，精子中的DJ-1水平会因暴露于精子毒物而降低。DJ-1也被鉴定为氢过氧化氢反应蛋白。最近，DJ-1的一个突变被发现与家族性帕金森病有关。在这里，我们介绍了DJ-1的晶体结构，其分辨率为1.95埃。DJ-1在晶体中形成二聚体，单体呈黄毒素样的Rossmann折叠。DJ-1在结构上与平谷热球菌胞内半胱氨酸蛋白酶I的单体亚单位最为相似，属于类谷氨酰胺转移酶超家族。然而，DJ-1在C-末端含有一个额外的α-螺旋，它阻断了DJ-1可能的催化位点，似乎调节了酶的活性。DJ-1可能诱导构象变化以获得氧化应激反应的催化活性。
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-Angstrom 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.