9B3A

filament of type 1 KD-mxyl miniature tau macrocycle derived from 4R tauopathic fold

9B3A の概要

• エントリーDOI: 10.2210/pdb9b3a/pdb
• EMDBエントリー: 44133
• 分子名称: Microtubule-associated protein tau, SER-VAL-GLN-ILE-VAL-TYR-LYS, AMINO GROUP, ... (4 entities in total)
• 機能のキーワード: tauopathies, neurodegenerative disorders, seed-competent miniature tau macrocycle, protein fibril
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 30
• 化学式量合計: 48027.34

構造登録者

Xu, X.,Angera, J.I.,Rajewski, H.B.,Jiang, W.,Del Valle, R.J. (登録日: 2024-03-18, 公開日: 2025-03-26, 最終更新日: 2025-10-08)

主引用文献

Angera, I.J.,Xu, X.,Rajewski, B.H.,Hallinan, G.I.,Zhang, X.,Ghetti, B.,Vidal, R.,Jiang, W.,Del Valle, J.R.
Macrocyclic beta-arch peptides that mimic the structure and function of disease-associated tau folds.
Nat.Chem., 17:865-874, 2025

PubMed Abstract: Tauopathies are a class of neurodegenerative disorders that feature tau protein aggregates in the brain. Misfolded tau has the capacity to seed the fibrillization of soluble tau, leading to the prion-like spread of aggregates. Within these filaments, tau protomers always exhibit a cross-β amyloid structure. However, distinct cross-β amyloid folds correlate with specific diseases. An understanding of how these conformations impact seeding activity remains elusive. Identifying the minimal epitopes required for transcellular propagation of tau aggregates represents a key step towards more relevant models of disease progression. Here we implement a diversity-oriented peptide macrocyclization approach towards miniature tau, or 'mini-tau', proteomimetics that can seed the aggregation of tau in engineered cells and primary neurons. Structural elucidation of one such seed-competent macrocycle reveals remarkable conformational congruence with core folds from patient-derived extracts of tau. The ability to impart β-arch form and function through peptide stapling has broad-ranging implications for the minimization and mimicry of pathological tau and other amyloid proteins that drive neurodegeneration.

PubMed: 40307419
DOI: 10.1038/s41557-025-01805-z

実験手法

ELECTRON MICROSCOPY (3.2 Å)