1UJJ

VHS domain of human GGA1 complexed with C-terminal peptide from BACE

1UJJ の概要

• エントリーDOI: 10.2210/pdb1ujj/pdb
• 関連するPDBエントリー: 1JWF 1JWG 1UJK
• 分子名称: ADP-ribosylation factor binding protein GGA1, C-terminal peptide from Beta-secretase (2 entities in total)
• 機能のキーワード: protein-peptide complex, protein transport, adaptor protein, protein transport-hydrolase complex, protein transport/hydrolase
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Golgi apparatus, trans-Golgi network membrane; Peripheral membrane protein: Q9UJY5; Membrane; Single-pass type I membrane protein: P56817
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 35019.37

構造登録者

Shiba, T.,Kametaka, S.,Kawasaki, M.,Shibata, M.,Waguri, S.,Uchiyama, Y.,Wakatsuki, S. (登録日: 2003-08-05, 公開日: 2004-05-11, 最終更新日: 2024-10-23)

主引用文献

Shiba, T.,Kametaka, S.,Kawasaki, M.,Shibata, M.,Waguri, S.,Uchiyama, Y.,Wakatsuki, S.
Insights into the Phosphoregulation of beta-Secretase Sorting Signal by the VHS Domain of GGA1
TRAFFIC, 5:437-448, 2004

PubMed Abstract: BACE (beta-site amyloid precursor protein cleaving enzyme, beta-secretase) is a type-I membrane protein which functions as an aspartic protease in the production of beta-amyloid peptide, a causative agent of Alzheimer's disease. Its cytoplasmic tail has a characteristic acidic-cluster dileucine motif recognized by the VHS domain of adaptor proteins, GGAs (Golgi-localizing, gamma-adaptin ear homology domain, ARF-interacting). Here we show that BACE is colocalized with GGAs in the trans-Golgi network and peripheral structures, and phosphorylation of a serine residue in the cytoplasmic tail enhances interaction with the VHS domain of GGA1 by about threefold. The X-ray crystal structure of the complex between the GGA1-VHS domain and the BACE C-terminal peptide illustrates a similar recognition mechanism as mannose 6-phosphate receptors except that a glutamine residue closes in to fill the gap created by the shorter BACE peptide. The serine and lysine of the BACE peptide point their side chains towards the solvent. However, phosphorylation of the serine affects the lysine side chain and the peptide backbone, resulting in one additional hydrogen bond and a stronger electrostatic interaction with the VHS domain, hence the reversible increase in affinity.

PubMed: 15117318
DOI: 10.1111/j.1600-0854.2004.00188.x

実験手法

X-RAY DIFFRACTION (2.6 Å)