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-Structure paper
タイトル | Two new polymorphic structures of human full-length alpha-synuclein fibrils solved by cryo-electron microscopy. |
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ジャーナル・号・ページ | Elife, Vol. 8, Year 2019 |
掲載日 | 2019年12月9日 |
著者 | Ricardo Guerrero-Ferreira / Nicholas Mi Taylor / Ana-Andreea Arteni / Pratibha Kumari / Daniel Mona / Philippe Ringler / Markus Britschgi / Matthias E Lauer / Ali Makky / Joeri Verasdonck / Roland Riek / Ronald Melki / Beat H Meier / Anja Böckmann / Luc Bousset / Henning Stahlberg / |
PubMed 要旨 | Intracellular inclusions rich in alpha-synuclein are a hallmark of several neuropathological diseases including Parkinson's disease (PD). Previously, we reported the structure of alpha-synuclein ...Intracellular inclusions rich in alpha-synuclein are a hallmark of several neuropathological diseases including Parkinson's disease (PD). Previously, we reported the structure of alpha-synuclein fibrils (residues 1-121), composed of two protofibrils that are connected via a densely-packed interface formed by residues 50-57 (Guerrero-Ferreira, eLife 218;7:e36402). We here report two new polymorphic atomic structures of alpha-synuclein fibrils termed polymorphs 2a and 2b, at 3.0 Å and 3.4 Å resolution, respectively. These polymorphs show a radically different structure compared to previously reported polymorphs. The new structures have a 10 nm fibril diameter and are composed of two protofilaments which interact via intermolecular salt-bridges between amino acids K45, E57 (polymorph 2a) or E46 (polymorph 2b). The non-amyloid component (NAC) region of alpha-synuclein is fully buried by previously non-described interactions with the N-terminus. A hydrophobic cleft, the location of familial PD mutation sites, and the nature of the protofilament interface now invite to formulate hypotheses about fibril formation, growth and stability. |
リンク | Elife / PubMed:31815671 / PubMed Central |
手法 | EM (らせん対称) |
解像度 | 2.98 - 3.46 Å |
構造データ | EMDB-10305, PDB-6sst: EMDB-10307, PDB-6ssx: |
由来 |
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キーワード | PROTEIN FIBRIL / amyloid / parkinson |