7LNA

Infectious mammalian prion fibril (263K scrapie)

7LNA の概要

• エントリーDOI: 10.2210/pdb7lna/pdb
• EMDBエントリー: 23459
• 分子名称: Major prion protein (1 entity in total)
• 機能のキーワード: infectious mammalian prion, templating, glycosylated glycophophatidlyinositol-anchored amyloid, piribs, protein fibril
• 由来する生物種: Mesocricetus auratus (Golden hamster)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 48792.30

構造登録者

Kraus, A.,Hoyt, F.,Schwartz, C.L.,Hansen, B.,Hughson, A.G.,Artikis, E.,Race, B.,Caughey, B. (登録日: 2021-02-06, 公開日: 2021-09-01, 最終更新日: 2024-11-06)

主引用文献

Kraus, A.,Hoyt, F.,Schwartz, C.L.,Hansen, B.,Artikis, E.,Hughson, A.G.,Raymond, G.J.,Race, B.,Baron, G.S.,Caughey, B.
High-resolution structure and strain comparison of infectious mammalian prions.
Mol.Cell, 81:4540-, 2021

PubMed Abstract: Within the extensive range of self-propagating pathologic protein aggregates of mammals, prions are the most clearly infectious (e.g., ∼10 lethal doses per milligram). The structures of such lethal assemblies of PrP molecules have been poorly understood. Here we report a near-atomic core structure of a brain-derived, fully infectious prion (263K strain). Cryo-electron microscopy showed amyloid fibrils assembled with parallel in-register intermolecular β sheets. Each monomer provides one rung of the ordered fibril core, with N-linked glycans and glycolipid anchors projecting outward. Thus, single monomers form the templating surface for incoming monomers at fibril ends, where prion growth occurs. Comparison to another prion strain (aRML) revealed major differences in fibril morphology but, like 263K, an asymmetric fibril cross-section without paired protofilaments. These findings provide structural insights into prion propagation, strains, species barriers, and membrane pathogenesis. This structure also helps frame considerations of factors influencing the relative transmissibility of other pathologic amyloids.

PubMed: 34433091
DOI: 10.1016/j.molcel.2021.08.011

実験手法

ELECTRON MICROSCOPY (3.14 Å)