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FEBS Lett. 2003 Aug 14;549(1-3):171-5.

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

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1
Department of Biochemistry and Biophysics and Lineberger Comprehensive Cancer Center, The University of North Carolina, Chapel Hill, NC 27599-7260, USA.

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 A 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.

PMID:
12914946
DOI:
10.1016/s0014-5793(03)00764-6
[Indexed for MEDLINE]
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