2LMP

Structural Model for a 40-residue Beta-Amyloid Fibril with Three-Fold Symmetry, Positive Stagger

2LMP の概要

• エントリーDOI: 10.2210/pdb2lmp/pdb
• 関連するPDBエントリー: 2LMN 2LMO 2LMQ
• NMR情報: BMRB: 18129
• 分子名称: Beta-amyloid protein 40 (1 entity in total)
• 機能のキーワード: alzheimer's disease, three-fold symmetry, protein fibril
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Membrane; Single-pass type I membrane protein: P05067
• タンパク質・核酸の鎖数: 18
• 化学式量合計: 78045.34

構造登録者

Tycko, R.,Paravastu, A. (登録日: 2011-12-08, 公開日: 2011-12-28, 最終更新日: 2024-05-01)

主引用文献

Paravastu, A.,Leapman, R.,Yau, W.,Tycko, R.
Molecular structural basis for polymorphism in Alzheimer's beta-amyloid fibrils
Proc.Natl.Acad.Sci.USA, 105:18349-18354, 2008

PubMed Abstract: We describe a full structural model for amyloid fibrils formed by the 40-residue beta-amyloid peptide associated with Alzheimer's disease (Abeta(1-40)), based on numerous constraints from solid state NMR and electron microscopy. This model applies specifically to fibrils with a periodically twisted morphology, with twist period equal to 120 +/- 20 nm (defined as the distance between apparent minima in fibril width in negatively stained transmission electron microscope images). The structure has threefold symmetry about the fibril growth axis, implied by mass-per-length data and the observation of a single set of (13)C NMR signals. Comparison with a previously reported model for Abeta(1-40) fibrils with a qualitatively different, striated ribbon morphology reveals the molecular basis for polymorphism. At the molecular level, the 2 Abeta(1-40) fibril morphologies differ in overall symmetry (twofold vs. threefold), the conformation of non-beta-strand segments, and certain quaternary contacts. Both morphologies contain in-register parallel beta-sheets, constructed from nearly the same beta-strand segments. Because twisted and striated ribbon morphologies are also observed for amyloid fibrils formed by other polypeptides, such as the amylin peptide associated with type 2 diabetes, these structural variations may have general implications.

PubMed: 19015532

実験手法

SOLID-STATE NMR