2LP1

The solution NMR structure of the transmembrane C-terminal domain of the amyloid precursor protein (C99)

2LP1 の概要

• エントリーDOI: 10.2210/pdb2lp1/pdb
• NMR情報: BMRB: 15775
• 分子名称: C99 (1 entity in total)
• 機能のキーワード: amyloid precursor protein c-terminal fragment, alzheimer's disease, membrane protein, amyloid-beta precursor, transmembrane protein
• 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: 1
• 化学式量合計: 13801.77

構造登録者

Barrett, P.J.,Song, Y.,Van Horn, W.D.,Hustedt, E.J.,Schafer, J.M.,Hadziselimovic, A.,Beel, A.J.,Sanders, C.R. (登録日: 2012-01-30, 公開日: 2012-06-06, 最終更新日: 2024-05-01)

主引用文献

Barrett, P.J.,Song, Y.,Van Horn, W.D.,Hustedt, E.J.,Schafer, J.M.,Hadziselimovic, A.,Beel, A.J.,Sanders, C.R.
The amyloid precursor protein has a flexible transmembrane domain and binds cholesterol.
Science, 336:1168-1171, 2012

PubMed Abstract: C99 is the transmembrane carboxyl-terminal domain of the amyloid precursor protein that is cleaved by γ-secretase to release the amyloid-β polypeptides, which are associated with Alzheimer's disease. Nuclear magnetic resonance and electron paramagnetic resonance spectroscopy show that the extracellular amino terminus of C99 includes a surface-embedded "N-helix" followed by a short "N-loop" connecting to the transmembrane domain (TMD). The TMD is a flexibly curved α helix, making it well suited for processive cleavage by γ-secretase. Titration of C99 reveals a binding site for cholesterol, providing mechanistic insight into how cholesterol promotes amyloidogenesis. Membrane-buried GXXXG motifs (G, Gly; X, any amino acid), which have an established role in oligomerization, were also shown to play a key role in cholesterol binding. The structure and cholesterol binding properties of C99 may aid in the design of Alzheimer's therapeutics.

PubMed: 22654059
DOI: 10.1126/science.1219988

実験手法

SOLUTION NMR