کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8965564 | 1646724 | 2018 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
A transient post-translational modification of active site cysteine alters binding properties of the parkinsonism protein DJ-1
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
Mutations in the human protein DJ-1 cause early onset of Parkinson's disease. A reactive cysteine residue (Cys106) 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 150â¯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 Cys106 is carboxymethylated in a fraction of DJ-1 tightly bound to Ni-NTA and that the replacement of Cys106 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 Cys106 that transforms into a Cys106-carboxymethyl adduct upon elution from Ni-NTA. We conclude that an unknown metabolite reacts with Cys106 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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 504, Issue 1, 26 September 2018, Pages 328-333
Journal: Biochemical and Biophysical Research Communications - Volume 504, Issue 1, 26 September 2018, Pages 328-333
نویسندگان
Arman Mussakhmetov, Igor A. Shumilin, Raushan Nugmanova, Ivan G. Shabalin, Timur Baizhumanov, Daulet Toibazar, Bekbolat Khassenov, Wladek Minor, Darkhan Utepbergenov,