Abstract
DJ-1, a protein that causes recessive early-onset Parkinson disease (PD), is believed to be destabilized in PD. Covalent dimerization of DJ-1, with cyclic disulfides, is a potential strategy to stabilize the protein while restoring its native homodimeric form. Here we attempt to elucidate more information about the underlying details of covalent dimerization, including its specificity. We also examine the effect of non-cyclic disulfide mediating binding to DJ-1 on the protein’s stability and investigate its specificity. We discover multiple methods of stabilizing DJ-1 selectively: either through covalent dimerization at Cys53 using a cyclic disulfide or covalent modification at Cys106 using a non-cyclic disulfide.