View source for 1uad


==Crystal structure of the RalA-GppNHp-Sec5 Ral-binding domain complex==
<StructureSection load='1uad' size='340' side='right'caption='[[1uad]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1uad]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UAD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1UAD FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1c1y|1c1y]], [[1he8|1he8]], [[1k8r|1k8r]], [[1lfd|1lfd]]</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=1uad FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1uad OCA], [http://pdbe.org/1uad PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1uad RCSB], [http://www.ebi.ac.uk/pdbsum/1uad PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1uad ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/RALA_HUMAN RALA_HUMAN]] Multifunctional GTPase involved in a variety of cellular processes including gene expression, cell migration, cell proliferation, oncogenic transformation and membrane trafficking. Accomplishes its multiple functions by interacting with distinct downstream effectors. Acts as a GTP sensor for GTP-dependent exocytosis of dense core vesicles. Plays a role in the early stages of cytokinesis and is required to tether the exocyst to the cytokinetic furrow. The RALA-exocyst complex regulates integrin-dependent membrane raft exocytosis and growth signaling. Key regulator of LPAR1 signaling and competes with ADRBK1 for binding to LPAR1 thus affecting the signaling properties of the receptor. Required for anchorage-independent proliferation of transformed cells.<ref>PMID:18756269</ref> <ref>PMID:19306925</ref> <ref>PMID:20005108</ref>  [[http://www.uniprot.org/uniprot/EXOC2_RAT EXOC2_RAT]] Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane. 
== 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/ua/1uad_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=1uad ConSurf].
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== Publication Abstract from PubMed ==
The sec6/8 complex or exocyst is an octameric protein complex that functions during cell polarization by regulating the site of exocytic vesicle docking to the plasma membrane, in concert with small GTP-binding proteins. The Sec5 subunit of the mammalian sec6/8 complex binds Ral in a GTP-dependent manner. Here we report the crystal structure of the complex between the Ral-binding domain of Sec5 and RalA bound to a non-hydrolyzable GTP analog (GppNHp) at 2.1 A resolution, providing the first structural insights into the mechanism and specificity of sec6/8 regulation. The Sec5 Ral-binding domain folds into an immunoglobulin-like beta-sandwich structure, which represents a novel fold for an effector of a GTP-binding protein. The interface between the two proteins involves a continuous antiparallel beta-sheet, similar to that found in other effector/G-protein complexes, such as Ras and Rap1A. Specific interactions unique to the RalA.Sec5 complex include Sec5 Thr11 and Arg27, and RalA Glu38, which we show are required for complex formation by isothermal titration calorimetry. Comparison of the structures of GppNHp- and GDP-bound RalA suggests a nucleotide-dependent switch mechanism for Sec5 binding.

Structural basis of the interaction between RalA and Sec5, a subunit of the sec6/8 complex.,Fukai S, Matern HT, Jagath JR, Scheller RH, Brunger AT EMBO J. 2003 Jul 1;22(13):3267-78. PMID:12839989<ref>PMID:12839989</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 1uad" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Buffalo rat]]
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Brunger, A T]]
[[Category: Fukai, S]]
[[Category: Matern, H T]]
[[Category: Scheller, R H]]
[[Category: Beta-sandwich]]
[[Category: Endocytosis-exocytosis complex]]
[[Category: Immunogloblin-like fold]]
[[Category: Small gtp-binding protein]]