Solid-state NMR structure of a pathogenic fibril of full-length human ?-synuclein [electronic resource]

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Tác giả:

Ngôn ngữ: eng

Ký hiệu phân loại: 547.6 Aromatic compounds

Thông tin xuất bản: Washington, D.C. : Oak Ridge, Tenn. : United States. Dept. of Energy. Office of Science ; Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy, 2016

Mô tả vật lý: Size: p. 409-415 : , digital, PDF file.

Bộ sưu tập: Metadata

ID: 260889

Misfolded ?-synuclein amyloid fibrils are the principal components of Lewy bodies and neurites, hallmarks of Parkinson's disease (PD). In this paper, we present a high-resolution structure of an ?-synuclein fibril, in a form that induces robust pathology in primary neuronal culture, determined by solid-state NMR spectroscopy and validated by EM and X-ray fiber diffraction. Over 200 unique long-range distance restraints define a consensus structure with common amyloid features including parallel, in-register ?-sheets and hydrophobic-core residues, and with substantial complexity arising from diverse structural features including an intermolecular salt bridge, a glutamine ladder, close backbone interactions involving small residues, and several steric zippers stabilizing a new orthogonal Greek-key topology. These characteristics contribute to the robust propagation of this fibril form, as supported by the structural similarity of early-onset-PD mutants. Finally, the structure provides a framework for understanding the interactions of ?-synuclein with other proteins and small molecules, to aid in PD diagnosis and treatment.
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