کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2189492 1096213 2006 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A Novel Mechanism of Interaction between α-Synuclein and Biological Membranes
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
A Novel Mechanism of Interaction between α-Synuclein and Biological Membranes
چکیده انگلیسی

Conformational abnormalities and aggregation of α-synuclein (α-syn) have been linked to the pathogenesis of Parkinson’s (PD) and related diseases. It has been shown that α-syn can stably bind artificial phospholipid vesicles through α-helix formation in its N-terminal repeat region. However, little is known about the membrane interaction in cells. In the current study, we determined the membrane-binding properties of α-syn to biological membranes by using bi-functional chemical crosslinkers, which allow the detection of transient, but specific, interactions. By utilizing various point mutations and deletions within α-syn, we demonstrated that the membrane interaction of α-syn in cells is also mediated by α-helix formation in the N-terminal repeat region. Moreover, the PD-linked A30P mutation causes reduced membrane binding, which is concordant with the artificial membrane studies. However, contrary to the interaction with artificial membranes, the interaction with biological membranes is rapidly reversible and is not driven by electrostatic attraction. Furthermore, the interaction of α-syn with cellular membranes occurs only in the presence of non-protein and non-lipid cytosolic components, which distinguishes it from the spontaneity of the interaction with artificial membranes. More interestingly, addition of the cytosolic preparation to artificial membranes resulted in the transient, charge-independent binding of α-syn similar to the interaction with biological membranes. These results suggest that in cells, α-syn is engaged in a fundamentally different mode of membrane interaction than the charge-dependent artificial membrane binding, and the mode of interaction is determined by the intrinsic properties of α-syn itself and by the cytoplasmic context.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular Biology - Volume 360, Issue 2, 7 July 2006, Pages 386–397
نویسندگان
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