View source for 1ujk


==VHS domain of human GGA1 complexed with C-terminal phosphopeptide from BACE==
<StructureSection load='1ujk' size='340' side='right'caption='[[1ujk]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1ujk]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UJK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1UJK FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1ujk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ujk OCA], [https://pdbe.org/1ujk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ujk RCSB], [https://www.ebi.ac.uk/pdbsum/1ujk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ujk ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GGA1_HUMAN GGA1_HUMAN] Plays a role in protein sorting and trafficking between the trans-Golgi network (TGN) and endosomes. Mediates the ARF-dependent recruitment of clathrin to the TGN and binds ubiquitinated proteins and membrane cargo molecules with a cytosolic acidic cluster-dileucine (AC-LL) motif.<ref>PMID:11301005</ref> 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/uj/1ujk_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1ujk ConSurf].
<div style="clear:both"></div>
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== Publication Abstract from PubMed ==
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.

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<ref>PMID:15117318</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1ujk" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Kametaka S]]
[[Category: Kawasaki M]]
[[Category: Shiba T]]
[[Category: Shibata M]]
[[Category: Uchiyama Y]]
[[Category: Waguri S]]
[[Category: Wakatsuki S]]