Wilson Mark A, St Amour Courtney V, Collins Jennifer L, Ringe Dagmar, Petsko Gregory A
Departments of Biochemistry and Chemistry, and Rosenstiel Basic Medical Sciences Research Center, Brandeis University, 415 South Street, MS 029, Waltham, MA 02454-9110, USA.
Proc Natl Acad Sci U S A. 2004 Feb 10;101(6):1531-6. doi: 10.1073/pnas.0308089100. Epub 2004 Jan 26.
The yeast gene YDR533C encodes a protein belonging to the DJ-1/ThiJ/PfpI superfamily. This family includes the human protein DJ-1, which is mutated in autosomal recessive early-onset Parkinson's disease. The function of DJ-1 and its yeast homologue YDR533Cp is unknown. We report here the crystal structure of YDR533Cp at 1.8-A resolution. The structure indicates that the closest relative to YDR533Cp is the Escherichia coli heat shock protein Hsp31 (YedU), which has both chaperone and protease activity. As expected, the overall fold of the core domain of YDR533Cp is also similar to that of DJ-1 and the bacterial protease PfpI. YDR533Cp contains a possible catalytic triad analogous to that of Hsp31 and an additional domain that is present in Hsp31 but is not seen in DJ-1 and other members of the family. The cysteine in this triad (Cys-138) is oxidized in this crystal structure, similar to modifications seen in the corresponding cysteine in the crystal structure of DJ-1. YDR533Cp appears to be a dimer both in solution and the crystal, but this dimer is formed by a different interface than that found in Hsp31 or other members of the superfamily.
酵母基因YDR533C编码一种属于DJ-1/ThiJ/PfpI超家族的蛋白质。该家族包括人类蛋白质DJ-1，它在常染色体隐性早发性帕金森病中发生突变。DJ-1及其酵母同源物YDR533Cp的功能尚不清楚。我们在此报告YDR533Cp在1.8埃分辨率下的晶体结构。该结构表明，与YDR533Cp关系最密切的是大肠杆菌热休克蛋白Hsp31（YedU），它具有伴侣和蛋白酶活性。正如预期的那样，YDR533Cp核心结构域的整体折叠也与DJ-1和细菌蛋白酶PfpI相似。YDR533Cp含有一个类似于Hsp31的可能的催化三联体以及一个在Hsp31中存在但在DJ-1和该家族其他成员中未发现的额外结构域。在该晶体结构中，这个三联体中的半胱氨酸（Cys-138）被氧化，类似于在DJ-1晶体结构中相应半胱氨酸中观察到的修饰。YDR533Cp在溶液和晶体中似乎都是二聚体，但这种二聚体是由与Hsp31或超家族其他成员不同的界面形成的。
