View source for 1jwg


==VHS Domain of human GGA1 complexed with cation-independent M6PR C-terminal Peptide==
<StructureSection load='1jwg' size='340' side='right'caption='[[1jwg]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1jwg]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JWG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1JWG FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1jwf|1jwf]]</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1jwg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jwg OCA], [http://pdbe.org/1jwg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1jwg RCSB], [http://www.ebi.ac.uk/pdbsum/1jwg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1jwg ProSAT]</span></td></tr>
</table>
== Function ==
[[http://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>  [[http://www.uniprot.org/uniprot/MPRI_HUMAN MPRI_HUMAN]] Transport of phosphorylated lysosomal enzymes from the Golgi complex and the cell surface to lysosomes. Lysosomal enzymes bearing phosphomannosyl residues bind specifically to mannose-6-phosphate receptors in the Golgi apparatus and the resulting receptor-ligand complex is transported to an acidic prelyosomal compartment where the low pH mediates the dissociation of the complex. This receptor also binds IGF2. Acts as a positive regulator of T-cell coactivation, by binding DPP4.<ref>PMID:10900005</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/jw/1jwg_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=1jwg ConSurf].
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== Publication Abstract from PubMed ==
GGAs (Golgi-localizing, gamma-adaptin ear homology domain, ARF-interacting proteins) are critical for the transport of soluble proteins from the trans-Golgi network (TGN) to endosomes/lysosomes by means of interactions with TGN-sorting receptors, ADP-ribosylation factor (ARF), and clathrin. The amino-terminal VHS domains of GGAs form complexes with the cytoplasmic domains of sorting receptors by recognizing acidic-cluster dileucine (ACLL) sequences. Here we report the X-ray structure of the GGA1 VHS domain alone, and in complex with the carboxy-terminal peptide of cation-independent mannose 6-phosphate receptor containing an ACLL sequence. The VHS domain forms a super helix with eight alpha-helices, similar to the VHS domains of TOM1 and Hrs. Unidirectional movements of helices alpha6 and alpha8, and some of their side chains, create a set of electrostatic and hydrophobic interactions for correct recognition of the ACLL peptide. This recognition mechanism provides the basis for regulation of protein transport from the TGN to endosomes/lysosomes, which is shared by sortilin and low-density lipoprotein receptor-related protein.

Structural basis for recognition of acidic-cluster dileucine sequence by GGA1.,Shiba T, Takatsu H, Nogi T, Matsugaki N, Kawasaki M, Igarashi N, Suzuki M, Kato R, Earnest T, Nakayama K, Wakatsuki S Nature. 2002 Feb 21;415(6874):937-41. PMID:11859376<ref>PMID:11859376</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 1jwg" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Earnest, T]]
[[Category: Igarashi, N]]
[[Category: Kato, R]]
[[Category: Kawasaki, M]]
[[Category: Matsugaki, N]]
[[Category: Nakayama, K]]
[[Category: Nogi, T]]
[[Category: Shiba, T]]
[[Category: Suzuki, M]]
[[Category: Takatsu, H]]
[[Category: Wakatsuki, S]]
[[Category: Protein transport-protein binding complex]]
[[Category: Protein-peptide complex]]
[[Category: Super helix]]