1UJJ

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

Summary for 1UJJ

• Entry DOI: 10.2210/pdb1ujj/pdb
• Related: 1JWF 1JWG 1UJK
• Descriptor: ADP-ribosylation factor binding protein GGA1, C-terminal peptide from Beta-secretase (2 entities in total)
• Functional Keywords: protein-peptide complex, protein transport, adaptor protein, protein transport-hydrolase complex, protein transport/hydrolase
• Biological source: Homo sapiens (human); More
• Cellular location: Golgi apparatus, trans-Golgi network membrane; Peripheral membrane protein: Q9UJY5; Membrane; Single-pass type I membrane protein: P56817
• Total number of polymer chains: 3
• Total formula weight: 35019.37

Authors

Shiba, T.,Kametaka, S.,Kawasaki, M.,Shibata, M.,Waguri, S.,Uchiyama, Y.,Wakatsuki, S. (deposition date: 2003-08-05, release date: 2004-05-11, Last modification date: 2024-10-23)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.6 Å)