کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2189335 1096207 2006 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Heat Shock Protein 70 Inhibits α-Synuclein Fibril Formation via Interactions with Diverse Intermediates
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Heat Shock Protein 70 Inhibits α-Synuclein Fibril Formation via Interactions with Diverse Intermediates
چکیده انگلیسی

α-Synuclein (AS) is a main component of Lewy bodies in midbrain dopamine neurons pathologically characteristic of Parkinson's disease. We show that heat shock protein (Hsp) 70 inhibits AS fibril formation via preventing the formation of prefibrillar AS (PreAS), binding with PreAS to impede nuclei formation, and binding with nuclei to retard fibril elongation. Also, Hsp70 suppresses the PreAS-induced permeabilization of vesicular membrane through interactions with PreAS. The substrate-binding domain alone is sufficient for Hsp70 to inhibit AS fibril formation. The binding of Hsp70 with PreAS only requires the substrate-binding subdomain, and the binding with AS nuclei requires the C-terminal lid subdomain as well. The results may form the molecular basis for elucidating the mechanism of AS fibril formation and the crucial roles of chaperones in protecting proteins from toxic conversion in many conformational diseases.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular Biology - Volume 364, Issue 3, 1 December 2006, Pages 323–336
نویسندگان
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