Identification and nanomechanical characterization of the fundamental single-strand protofilaments of amyloid alpha-synuclein fibrils

Ruggeri Francesco Simone; Benedetti Fabrizio; Knowles Tuomas P. J.Lashuel Hilal A.Sekatskii SergeyDietler Giovanni

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Identification and nanomechanical characterization of the fundamental single-strand protofilaments of amyloid alpha-synuclein fibrils

机译：Identification and nanomechanical characterization of the fundamental single-strand protofilaments of amyloid alpha-synuclein fibrils

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The formation and spreading of amyloid aggregates from the presynaptic protein alpha-synuclein in the brain play central roles in the pathogenesis of Parkinson's disease. Here, we use high-resolution atomic force microscopy to investigate the early oligomerization events of alpha-synuclein with single monomer angstrom resolution. We identify, visualize, and characterize directly the smallest elementary unit in the hierarchical assembly of amyloid fibrils, termed here single-strand protofilaments. We show that protofilaments form from the direct molecular assembly of unfolded monomeric alpha-synuclein polypeptide chains. To unravel protofilaments' internal structure and elastic properties, we manipulated nano-mechanically these species by atomic force spectroscopy. The single-molecule scale identification and characterization of the fundamental unit of amyloid assemblies provide insights into early events underlying their formation and shed light on opportunities for therapeutic intervention at the early stages of aberrant protein self-assembly.

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《Proceedings of the National Academy of Sciences of the United States of America.》 |2018年第28期|7230-7235|共6页
作者
Ruggeri Francesco Simone; Benedetti Fabrizio; Knowles Tuomas P. J.Lashuel Hilal A.Sekatskii SergeyDietler Giovanni;
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作者单位

Univ Lausanne, Ctr Integrat Genom, Fac Biol & Med, CH-1015 Lausanne, Switzerland;

Univ Cambridge, Dept Chem, Cambridge CB2 1EW, England;

Ecole Polytech Fed Lausanne, Brain Mind Inst, Fac Life Sci, Lab Mol & Chem Biol Neurodegenerat, CH-1015 Lausanne, SwitzerlandEcole Polytech Fed Lausanne, Lab Phys Living Matter, CH-1015 Lausanne, Switzerland;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
amyloid; protein aggregation; atomic force microscopy; early molecular assembly; force spectroscopy;

Identification and nanomechanical characterization of the fundamental single-strand protofilaments of amyloid alpha-synuclein fibrils

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