4BXL

Structure of alpha-synuclein in complex with an engineered binding protein

4BXL の概要

• エントリーDOI: 10.2210/pdb4bxl/pdb
• 分子名称: AS69, ALPHA SYNUCLEIN (2 entities in total)
• 機能のキーワード: fibril, amyloid, parkinson's disease, protein aggregation, protein engineering, protein misfolding, scaffold proteins
• 由来する生物種: SYNTHETIC CONSTRUCT; 詳細
• 細胞内の位置: Cytoplasm: P37840
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 12380.70

構造登録者

Mirecka, E.A.,Shaykhalishahi, H.,Lecher, J.,Stoldt, M.,Hoyer, W. (登録日: 2013-07-12, 公開日: 2014-05-21, 最終更新日: 2024-10-09)

主引用文献

Mirecka, E.A.,Shaykhalishahi, H.,Gauhar, A.,Akgul, S.,Lecher, J.,Willbold, D.,Stoldt, M.,Hoyer, W.
Sequestration of a Beta-Hairpin for Control of Alpha-Synuclein Aggregation.
Angew.Chem.Int.Ed.Engl., 53:4227-, 2014

PubMed Abstract: The misfolding and aggregation of the protein α-synuclein (α-syn), which results in the formation of amyloid fibrils, is involved in the pathogenesis of Parkinson's disease and other synucleinopathies. The emergence of amyloid toxicity is associated with the formation of partially folded aggregation intermediates. Here, we engineered a class of binding proteins termed β-wrapins (β-wrap proteins) with affinity for α-synuclein (α-syn). The NMR structure of an α-syn:β-wrapin complex reveals a β-hairpin of α-syn comprising the sequence region α-syn(37-54). The β-wrapin inhibits α-syn aggregation and toxicity at substoichiometric concentrations, demonstrating that it interferes with the nucleation of aggregation.

PubMed: 24623599
DOI: 10.1002/ANIE.201309001

実験手法

SOLUTION NMR