Crystal structure of human DJ-1, a protein associated with early onset Parkinson's disease
Crystal structure of human DJ-1, a protein associated with early onset Parkinson's disease
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DOI：
10.1074/jbc.m304221200
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发表时间：
2003-08-15
影响因子：
4.8
通讯作者：
Tong, L
中科院分区：
文献类型：
--
作者：
Tao, X;Tong, L
我们报告了人类DJ-1的1.8埃分辨率的晶体结构，这与早发性帕金森病有关。DJ-1的单体含有在DJ-1/ThiJ/ PfpI超家族成员中保守的α/β折叠。然而，该结构在C末端还包含一个额外的螺旋，这介导了DJ-1蛋白质的一种新的二聚化模式。在二聚体界面附近发现了一个推定的活性位点，其中Cys-106、His-126和Glu-18残基可能在该蛋白的催化作用中起重要作用。对致病性L166 P突变体的研究表明，该突变破坏了C-末端区域和蛋白质的二聚化。DJ-1蛋白可能仅作为二聚体起作用。在残基130（DJ-1的类小泛素化位点）处的Lys至Arg突变对蛋白质的结构具有最小的影响。
We report the crystal structure at 1.8-Angstrom resolution of human DJ-1, which has been linked to early onset Parkinson's disease. The monomer of DJ-1 contains the alpha/beta-fold that is conserved among members of the DJ-1/ThiJ/ PfpI superfamily. However, the structure also contains an extra helix at the C terminus, which mediates a novel mode of dimerization for the DJ-1 proteins. A putative active site has been identified near the dimer interface, and the residues Cys-106, His-126, and Glu-18 may play important roles in the catalysis by this protein. Studies with the disease-causing L166P mutant suggest that the mutation has disrupted the C-terminal region and the dimerization of the protein. The DJ-1 proteins may function only as dimers. The Lys to Arg mutation at residue 130, the site of sumoylation of DJ-1, has minimal impact on the structure of the protein.