PDBsum entry: 1ujj

Protein transport/hydrolase

PDB id: 1ujj

Contents

Protein chains

140 a.a. *

Ligands

ASP-ASP-ILE-SER-LEU-LEU-LYS

* Residue conservation analysis

PDB id:

1ujj

Name:

Protein transport/hydrolase

Title:

Vhs domain of human gga1 complexed with c-terminal peptide from bace

Structure:

Adp-ribosylation factor binding protein gga1. Chain: a, b. Fragment: vhs domain, n-terminal domain. Synonym: gga1. Engineered: yes. C-terminal peptide from beta-secretase. Chain: c. Synonym: c-terminal peptide from bace. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693. Synthetic: yes. Other_details: synthesized peptide

Biol. unit:

Trimer (from PQS)

Resolution:

2.60Å R-factor: 0.244 R-free: 0.295

Authors:

T.Shiba,S.Kametaka,M.Kawasaki,M.Shibata,S.Waguri,Y.Uchiyama, S.Wakatsuki

Key ref:

T.Shiba et al. (2004). Insights into the phosphoregulation of beta-secretase sorting signal by the VHS domain of GGA1. Traffic, 5, 437-448. PubMed id: 15117318 DOI: 10.1111/j.1600-0854.2004.00188.x

Date:

05-Aug-03 Release date: 11-May-04

Protein chains

Q9UJY5  (GGA1_HUMAN) -  ADP-ribosylation factor-binding protein GGA1

Seq: 639 a.a.

Struc: 140 a.a.

 Gene Ontology (GO) functional annotation 

• Biological process: intracellular protein transport (1 term)

DOI no: 10.1111/j.1600-0854.2004.00188.x

Traffic 5:437-448 (2004)

PubMed id: 15117318

Insights into the phosphoregulation of beta-secretase sorting signal by the VHS domain of GGA1.

T.Shiba, S.Kametaka, M.Kawasaki, M.Shibata, S.Waguri, Y.Uchiyama, S.Wakatsuki.

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.