1ujk

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[[Image:1ujk.gif|left|200px]]
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{{Seed}}
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[[Image:1ujk.png|left|200px]]
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{{STRUCTURE_1ujk| PDB=1ujk | SCENE= }}
{{STRUCTURE_1ujk| PDB=1ujk | SCENE= }}
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'''VHS domain of human GGA1 complexed with C-terminal phosphopeptide from BACE'''
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===VHS domain of human GGA1 complexed with C-terminal phosphopeptide from BACE===
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==Overview==
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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.
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The line below this paragraph, {{ABSTRACT_PUBMED_15117318}}, adds the Publication Abstract to the page
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(as it appears on PubMed at http://www.pubmed.gov), where 15117318 is the PubMed ID number.
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{{ABSTRACT_PUBMED_15117318}}
==About this Structure==
==About this Structure==
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[[Category: Protein transport]]
[[Category: Protein transport]]
[[Category: Protein-peptide complex]]
[[Category: Protein-peptide complex]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 11:18:44 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 03:10:07 2008''

Revision as of 00:10, 29 July 2008

Image:1ujk.png

Template:STRUCTURE 1ujk

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

Template:ABSTRACT PUBMED 15117318

About this Structure

1UJK is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Insights into the phosphoregulation of beta-secretase sorting signal by the VHS domain of GGA1., Shiba T, Kametaka S, Kawasaki M, Shibata M, Waguri S, Uchiyama Y, Wakatsuki S, Traffic. 2004 Jun;5(6):437-48. PMID:15117318

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