کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2829569 1162814 2006 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Mechanical manipulation of Alzheimer’s amyloid β1–42 fibrils
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شناسی مولکولی
پیش نمایش صفحه اول مقاله
Mechanical manipulation of Alzheimer’s amyloid β1–42 fibrils
چکیده انگلیسی

The 39- to 42-residue-long amyloid β-peptide (Aβ-peptide) forms filamentous structures in the neuritic plaques found in the neuropil of Alzheimer’s disease patients. The assembly and deposition of Aβ-fibrils is one of the most important factors in the pathogenesis of this neurodegenerative disease. Although the structural analysis of amyloid fibrils is difficult, single-molecule methods may provide unique insights into their characteristics. In the present work, we explored the nanomechanical properties of amyloid fibrils formed from the full-length, most neurotoxic Aβ1–42 peptide, by manipulating individual fibrils with an atomic force microscope. We show that Aβ-subunit sheets can be mechanically unzipped from the fibril surface with constant forces in a reversible transition. The fundamental unzipping force (∼23 pN) was significantly lower than that observed earlier for fibrils formed from the Aβ1–40 peptide (∼33 pN), suggesting that the presence of the two extra residues (Ile and Ala) at the peptide’s C-terminus result in a mechanical destabilization of the fibril. Deviations from the constant force transition may arise as a result of geometrical constraints within the fibril caused by its left-handed helical structure. The nanomechanical fingerprint of the Aβ1–42 is further influenced by the structural dynamics of intrafibrillar interactions.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Structural Biology - Volume 155, Issue 2, August 2006, Pages 316–326
نویسندگان
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