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Cryo-EM structure of alpha-synuclein fibrils
Parkinson’s disease is a progressive neuropathological disorder that belongs to the class of synucleinopathies, in which the protein alpha-synuclein is found at abnormally high concentrations in affected neurons. Its hallmark are intracellular inclusions called Lewy bodies and Lewy neurites. We here...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6092118/ https://www.ncbi.nlm.nih.gov/pubmed/29969391 http://dx.doi.org/10.7554/eLife.36402 |
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author | Guerrero-Ferreira, Ricardo Taylor, Nicholas MI Mona, Daniel Ringler, Philippe Lauer, Matthias E Riek, Roland Britschgi, Markus Stahlberg, Henning |
author_facet | Guerrero-Ferreira, Ricardo Taylor, Nicholas MI Mona, Daniel Ringler, Philippe Lauer, Matthias E Riek, Roland Britschgi, Markus Stahlberg, Henning |
author_sort | Guerrero-Ferreira, Ricardo |
collection | PubMed |
description | Parkinson’s disease is a progressive neuropathological disorder that belongs to the class of synucleinopathies, in which the protein alpha-synuclein is found at abnormally high concentrations in affected neurons. Its hallmark are intracellular inclusions called Lewy bodies and Lewy neurites. We here report the structure of cytotoxic alpha-synuclein fibrils (residues 1–121), determined by cryo-electron microscopy at a resolution of 3.4 Å. Two protofilaments form a polar fibril composed of staggered β-strands. The backbone of residues 38 to 95, including the fibril core and the non-amyloid component region, are well resolved in the EM map. Residues 50–57, containing three of the mutation sites associated with familial synucleinopathies, form the interface between the two protofilaments and contribute to fibril stability. A hydrophobic cleft at one end of the fibril may have implications for fibril elongation, and invites for the design of molecules for diagnosis and treatment of synucleinopathies. |
format | Online Article Text |
id | pubmed-6092118 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-60921182018-08-15 Cryo-EM structure of alpha-synuclein fibrils Guerrero-Ferreira, Ricardo Taylor, Nicholas MI Mona, Daniel Ringler, Philippe Lauer, Matthias E Riek, Roland Britschgi, Markus Stahlberg, Henning eLife Neuroscience Parkinson’s disease is a progressive neuropathological disorder that belongs to the class of synucleinopathies, in which the protein alpha-synuclein is found at abnormally high concentrations in affected neurons. Its hallmark are intracellular inclusions called Lewy bodies and Lewy neurites. We here report the structure of cytotoxic alpha-synuclein fibrils (residues 1–121), determined by cryo-electron microscopy at a resolution of 3.4 Å. Two protofilaments form a polar fibril composed of staggered β-strands. The backbone of residues 38 to 95, including the fibril core and the non-amyloid component region, are well resolved in the EM map. Residues 50–57, containing three of the mutation sites associated with familial synucleinopathies, form the interface between the two protofilaments and contribute to fibril stability. A hydrophobic cleft at one end of the fibril may have implications for fibril elongation, and invites for the design of molecules for diagnosis and treatment of synucleinopathies. eLife Sciences Publications, Ltd 2018-07-03 /pmc/articles/PMC6092118/ /pubmed/29969391 http://dx.doi.org/10.7554/eLife.36402 Text en © 2018, Guerrero-Ferreira et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Neuroscience Guerrero-Ferreira, Ricardo Taylor, Nicholas MI Mona, Daniel Ringler, Philippe Lauer, Matthias E Riek, Roland Britschgi, Markus Stahlberg, Henning Cryo-EM structure of alpha-synuclein fibrils |
title | Cryo-EM structure of alpha-synuclein fibrils |
title_full | Cryo-EM structure of alpha-synuclein fibrils |
title_fullStr | Cryo-EM structure of alpha-synuclein fibrils |
title_full_unstemmed | Cryo-EM structure of alpha-synuclein fibrils |
title_short | Cryo-EM structure of alpha-synuclein fibrils |
title_sort | cryo-em structure of alpha-synuclein fibrils |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6092118/ https://www.ncbi.nlm.nih.gov/pubmed/29969391 http://dx.doi.org/10.7554/eLife.36402 |
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