4DBB

The PTB domain of Mint1 is autoinhibited by a helix in the C-terminal linker region

4DBB の概要

• エントリーDOI: 10.2210/pdb4dbb/pdb
• 分子名称: Amyloid beta A4 precursor protein-binding family A member 1, CHLORIDE ION, ACETIC ACID, ... (6 entities in total)
• 機能のキーワード: x11s/mints, ptb domain, chimera protein, protein transport
• 由来する生物種: Rattus norvegicus (Rat); 詳細
• 細胞内の位置: Cytoplasm . Isoform 2: Golgi apparatus : O35430
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 18868.80

構造登録者

Tomchick, D.R.,Rizo, J.,Ho, A.,Xu, Y. (登録日: 2012-01-13, 公開日: 2012-03-07, 最終更新日: 2024-02-28)

主引用文献

Matos, M.F.,Xu, Y.,Dulubova, I.,Otwinowski, Z.,Richardson, J.M.,Tomchick, D.R.,Rizo, J.,Ho, A.
Autoinhibition of Mint1 adaptor protein regulates amyloid precursor protein binding and processing.
Proc.Natl.Acad.Sci.USA, 109:3802-3807, 2012

PubMed Abstract: Mint adaptor proteins bind to the amyloid precursor protein (APP) and regulate APP processing associated with Alzheimer's disease; however, the molecular mechanisms underlying Mint regulation in APP binding and processing remain unclear. Biochemical, biophysical, and cellular experiments now show that the Mint1 phosphotyrosine binding (PTB) domain that binds to APP is intramolecularly inhibited by the adjacent C-terminal linker region. The crystal structure of a C-terminally extended Mint1 PTB fragment reveals that the linker region forms a short α-helix that folds back onto the PTB domain and sterically hinders APP binding. This intramolecular interaction is disrupted by mutation of Tyr633 within the Mint1 autoinhibitory helix leading to enhanced APP binding and β-amyloid production. Our findings suggest that an autoinhibitory mechanism in Mint1 is important for regulating APP processing and may provide novel therapies for Alzheimer's disease.

PubMed: 22355143
DOI: 10.1073/pnas.1119075109

実験手法

X-RAY DIFFRACTION (1.901 Å)