Crystal structure of DJ‐1/RS and implication on familial Parkinson's disease

FEBS Letters

Robinson, Howard²  Wang, Huanchen¹  Sun, Yingjie¹  Huai, Qing¹  Chin, Lih-Shen³  Li, Lian³  Ke, Hengming¹ 

[1] Department of Biochemistry and Biophysics and Lineberger Comprehensive Cancer Center, The University of North Carolina, Chapel Hill, NC 27599-7260, USA;Biology Department, Brookhaven National Laboratory, Upton, NY 11973-5000, USA;Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30332-3090, USA

关键词: Crystal structure;    Breast cancer;    Parkinson's disease;    Male fertility;    Protein inhibitor of activated STAT;    Androgen receptor;    PD;    Parkinson's disease;    CAP1;    contraception-associated protein 1;    SeDJ-1;    selenomethionyl DJ-1;    DJBP;    DJ-1-binding protein;    PIAS;    protein inhibitor of activated STAT;    AR;    androgen receptor;    SUMO;    small ubiquitin-related modifier;   

DOI  :  10.1016/S0014-5793(03)00764-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

DJ-1 is a protein involved in multiple physiological processes, including cancer, Parkinson's disease, and male fertility. It is unknown how DJ-1 functions in the apparently different systems. The crystal structure of DJ-1 at 1.6 Å resolution shows that DJ-1 is a helix-strand-helix sandwich and forms a dimer. The DJ-1 structure is similar to the members of the intracellular protease PfpI family. However, the catalytic triad of Cys–His–Glu is not strictly conserved in DJ-1, implying that DJ-1 has a different catalytic mechanism if it acts as a protease or DJ-1 serves as a regulatory protein in the physiological processes. The structure shows that Leu166 positions in the middle of a helix and thus predicts that the L166P mutation will bend the helix and impact the dimerization of DJ-1. As a result, the conformational changes may diminish the DJ-1 binding with its partner, leading to the familial Parkinson's disease caused by the single L166P mutation.

【 授权许可】

Unknown