+検索条件
-Structure paper
タイトル | The hereditary mutation G51D unlocks a distinct fibril strain transmissible to wild-type α-synuclein. |
---|---|
ジャーナル・号・ページ | Nat Commun, Vol. 12, Issue 1, Page 6252, Year 2021 |
掲載日 | 2021年10月29日 |
著者 | Yunpeng Sun / Houfang Long / Wencheng Xia / Kun Wang / Xia Zhang / Bo Sun / Qin Cao / Yaoyang Zhang / Bin Dai / Dan Li / Cong Liu / |
PubMed 要旨 | α-Synuclein (α-Syn) can form different fibril strains with distinct polymorphs and neuropathologies, which is associated with the clinicopathological variability in synucleinopathies. How different ...α-Synuclein (α-Syn) can form different fibril strains with distinct polymorphs and neuropathologies, which is associated with the clinicopathological variability in synucleinopathies. How different α-syn fibril strains are produced and selected under disease conditions remains poorly understood. In this study, we show that the hereditary mutation G51D induces α-syn to form a distinct fibril strain in vitro. The cryogenic electron microscopy (cryo-EM) structure of the G51D fibril strain was determined at 2.96 Å resolution. The G51D fibril displays a relatively small and extended serpentine fold distinct from other α-syn fibril structures. Moreover, we show by cryo-EM that wild-type (WT) α-syn can assembly into the G51D fibril strain via cross-seeding with G51D fibrils. Our study reveals a distinct structure of G51D fibril strain triggered by G51D mutation but feasibly adopted by both WT and G51D α-syn, which suggests the cross-seeding and strain selection of WT and mutant α-syn in familial Parkinson's disease (fPD). |
リンク | Nat Commun / PubMed:34716315 / PubMed Central |
手法 | EM (らせん対称) |
解像度 | 3.02 Å |
構造データ | EMDB-30931, PDB-7e0f: |
由来 |
|
キーワード | PROTEIN FIBRIL / amyloid fibril |