Crystal structure of DJ‐1/RS and implication on familial Parkinson's disease1

Abstract

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.