کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1235631 1495270 2012 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The acidic pH-induced structural changes in Pin1 as revealed by spectral methodologies
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آنالیزی یا شیمی تجزیه
پیش نمایش صفحه اول مقاله
The acidic pH-induced structural changes in Pin1 as revealed by spectral methodologies
چکیده انگلیسی

Pin1 is closely associated with the pathogenesis of cancers and Alzheimer’s disease (AD). Previously, we have shown the characteristics of the thermal denaturation of Pin1. Herein, the acid-induced denaturation of Pin1 was determined by means of fluorescence emission, synchronous fluorescence, far-UV CD, ANS fluorescence and RLS spectroscopies. The fluorescence emission spectra and the synchronous fluorescence spectra suggested the partially reversible unfolding (approximately from pH 7.0 to 4.0) and refolding (approximately from pH 4.0 to 1.0) of the structures around the chromophores in Pin1, apparently with an intermediate state at about pH 4.0–4.5. The far-UV CD spectra indicated that acidic pH (below pH 4.0) induced the structural transition from α-helix and random coils to β-sheet in Pin1. The ANS fluorescence and the RLS spectra further suggested the exposure of the hydrophobic side-chains of Pin1 and the aggregation of it especially below pH 2.3, and the aggregation possibly resulted in the formation of extra intermolecular β-sheet. The present work primarily shows that acidic pH can induce kinds of irreversible structural changes in Pin1, such as the exposure of the hydrophobic side-chains, the transition from α-helix to β-sheet and the aggregation of Pin1, and also explains why Pin1 loses most of its activity below pH 5.0. The results emphasize the important role of decreased pH in the pathogenesis of some Pin1-related diseases, and support the therapeutic approach for them by targeting acidosis and modifying the intracellular pH gradients.

Figure optionsDownload as PowerPoint slideHighlights
► We studied the acid-induced denaturation of Pin1 by spectral methodologies.
► Acidic pH induces the partially reversible unfolding and refolding of Pin1.
► Acidic pH induces the structural transition from α-helix to β-sheet in Pin1.
► Acidic pH induces the aggregation of the hydrophobic side-chains of Pin1.
► The aggregation of Pin1 possibly results in the intermolecular β-sheet.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy - Volume 98, December 2012, Pages 199–206
نویسندگان
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