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| | <StructureSection load='1uad' size='340' side='right'caption='[[1uad]], [[Resolution|resolution]] 2.10Å' scene=''> | | <StructureSection load='1uad' size='340' side='right'caption='[[1uad]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1uad]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat] and [https://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 [https://proteopedia.org/fgij/fg.htm?mol=1UAD FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1uad]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. 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 [https://proteopedia.org/fgij/fg.htm?mol=1UAD FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1c1y|1c1y]], [[1he8|1he8]], [[1k8r|1k8r]], [[1lfd|1lfd]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=1uad FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1uad OCA], [https://pdbe.org/1uad PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1uad RCSB], [https://www.ebi.ac.uk/pdbsum/1uad PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1uad ProSAT]</span></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=1uad FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1uad OCA], [https://pdbe.org/1uad PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1uad RCSB], [https://www.ebi.ac.uk/pdbsum/1uad PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1uad ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://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> [[https://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.
| + | [https://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> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Buffalo rat]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Brunger, A T]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Fukai, S]] | + | [[Category: Brunger AT]] |
| - | [[Category: Matern, H T]] | + | [[Category: Fukai S]] |
| - | [[Category: Scheller, R H]] | + | [[Category: Matern HT]] |
| - | [[Category: Beta-sandwich]] | + | [[Category: Scheller RH]] |
| - | [[Category: Endocytosis-exocytosis complex]]
| + | |
| - | [[Category: Immunogloblin-like fold]]
| + | |
| - | [[Category: Small gtp-binding protein]]
| + | |
| Structural highlights
Function
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.[1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
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[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Cascone I, Selimoglu R, Ozdemir C, Del Nery E, Yeaman C, White M, Camonis J. Distinct roles of RalA and RalB in the progression of cytokinesis are supported by distinct RalGEFs. EMBO J. 2008 Sep 17;27(18):2375-87. doi: 10.1038/emboj.2008.166. Epub 2008 Aug, 28. PMID:18756269 doi:http://dx.doi.org/10.1038/emboj.2008.166
- ↑ Aziziyeh AI, Li TT, Pape C, Pampillo M, Chidiac P, Possmayer F, Babwah AV, Bhattacharya M. Dual regulation of lysophosphatidic acid (LPA1) receptor signalling by Ral and GRK. Cell Signal. 2009 Jul;21(7):1207-17. doi: 10.1016/j.cellsig.2009.03.011. Epub, 2009 Mar 21. PMID:19306925 doi:10.1016/j.cellsig.2009.03.011
- ↑ Balasubramanian N, Meier JA, Scott DW, Norambuena A, White MA, Schwartz MA. RalA-exocyst complex regulates integrin-dependent membrane raft exocytosis and growth signaling. Curr Biol. 2010 Jan 12;20(1):75-9. doi: 10.1016/j.cub.2009.11.016. Epub 2009 Dec , 10. PMID:20005108 doi:http://dx.doi.org/10.1016/j.cub.2009.11.016
- ↑ Fukai S, Matern HT, Jagath JR, Scheller RH, Brunger AT. Structural basis of the interaction between RalA and Sec5, a subunit of the sec6/8 complex. EMBO J. 2003 Jul 1;22(13):3267-78. PMID:12839989 doi:10.1093/emboj/cdg329
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