Biochemistry, Biophysics, and Structural Biology Commons^™

Use Of Cysteine-Reactive Crosslinkers To Probe Conformational Flexibility Of Human Dj-1 Demonstrates That Glu18 Mutations Are Dimers, Janani Prahlad, David N. Hauser, Nicole M. Milkovic, Mark R. Cookson, Mark A. Wilson

Department of Biochemistry: Faculty Publications

The oxidation of a key cysteine residue (Cys106) in the parkinsonism-associated protein DJ-1 regulates its ability to protect against oxidative stress and mitochondrial damage. Cys106 interacts with a neighboring protonated Glu18 residue, stabilizing the Cys106-SO₂ ⁻ (sulfinic acid) form of DJ-1. To study this important post-translational modification, we previously designed several Glu18 mutations (E18N, E18D, E18Q) that alter the oxidative propensity of Cys106. However, recent results suggest these Glu18 mutations cause loss of DJ-1 dimerization, which would severely compromise the protein’s function. The purpose of this study was to conclusively determine the oligomerization state of these mutants using X-ray …