6M8Z

Crystal structure of human DJ-1 without a modification on Cys-106

Summary for 6M8Z

• Entry DOI: 10.2210/pdb6m8z/pdb
• Related: 6E5Z
• Descriptor: Protein/nucleic acid deglycase DJ-1, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: the exact function of this protein is still unknown, unknown function
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 20318.94

Authors

Shumilin, I.A.,Shabalin, I.G.,Shumilina, S.V.,Werenskjold, C.,Utepbergenov, D.,Minor, W. (deposition date: 2018-08-22, release date: 2018-09-05, Last modification date: 2023-10-11)

Primary citation

Mussakhmetov, A.,Shumilin, I.A.,Nugmanova, R.,Shabalin, I.G.,Baizhumanov, T.,Toibazar, D.,Khassenov, B.,Minor, W.,Utepbergenov, D.
A transient post-translational modification of active site cysteine alters binding properties of the parkinsonism protein DJ-1.
Biochem. Biophys. Res. Commun., 504:328-333, 2018

PubMed Abstract: Mutations in the human protein DJ-1 cause early onset of Parkinson's disease. A reactive cysteine residue (Cys) of DJ-1 is crucial for its protective function, although the underlying mechanisms are unclear. Here we show that a fraction of bacterially expressed polyhistidine-tagged human DJ-1 could not be eluted from a Ni-nitrilotriacetate (Ni-NTA) column with 150 mM imidazole. This unusually tight binding was accompanied by the appearance of blue violet color on the Ni-NTA column. We demonstrate by X-ray crystallography that Cys is carboxymethylated in a fraction of DJ-1 tightly bound to Ni-NTA and that the replacement of Cys by serine abrogates the tight binding and the appearance of blue violet color. However, carboxymethylation of purified DJ-1 is insufficient to confer the tight binding to Ni-NTA. Moreover, when eluted protein was re-applied to the Ni-NTA column, no tight binding was observed, indicating that the formation of high affinity complex with Ni-NTA depends on a transient modification of Cys that transforms into a Cys-carboxymethyl adduct upon elution from Ni-NTA. We conclude that an unknown metabolite reacts with Cys of DJ-1 to result in a transient post-translational modification. This modification is distinct from simple oxidation to sulfinic or sulfenic acids and confers altered binding properties to DJ-1 suggesting that it could serve as a signal for sensing oxidant stress.

PubMed: 30190129
DOI: 10.1016/j.bbrc.2018.08.190

Experimental method

X-RAY DIFFRACTION (1.83 Å)