2a78: Difference between revisions
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==Crystal structure of the C3bot-RalA complex reveals a novel type of action of a bacterial exoenzyme== | |||
<StructureSection load='2a78' size='340' side='right'caption='[[2a78]], [[Resolution|resolution]] 1.81Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2a78]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridium_botulinum_D_phage Clostridium botulinum D phage] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2A78 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2A78 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]] 1.81Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</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=2a78 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2a78 OCA], [https://pdbe.org/2a78 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2a78 RCSB], [https://www.ebi.ac.uk/pdbsum/2a78 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2a78 ProSAT]</span></td></tr> | |||
</table> | |||
== 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> | |||
== 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/a7/2a78_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=2a78 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
C3 exoenzymes from bacterial pathogens ADP-ribosylate and inactivate low-molecular-mass GTPases of the Rho subfamily. Ral, a Ras subfamily GTPase, binds the C3 exoenzymes from Clostridium botulinum and C. limosum with high affinity without being a substrate for ADP ribosylation. In the complex, the ADP-ribosyltransferase activity of C3 is blocked, while binding of NAD and NAD-glycohydrolase activity remain. Here we report the crystal structure of C3 from C. botulinum in a complex with GDP-bound RalA at 1.8 A resolution. C3 binds RalA with a helix-loop-helix motif that is adjacent to the active site. A quaternary complex with NAD suggests a mode for ADP-ribosyltransferase inhibition. Interaction of C3 with RalA occurs at a unique interface formed by the switch-II region, helix alpha3 and the P loop of the GTPase. C3-binding stabilizes the GDP-bound conformation of RalA and blocks nucleotide release. Our data indicate that C. botulinum exoenzyme C3 is a single-domain toxin with bifunctional properties targeting Rho GTPases by ADP ribosylation and Ral by a guanine nucleotide dissociation inhibitor-like effect, which blocks nucleotide exchange. | |||
Crystal structure of the C3bot-RalA complex reveals a novel type of action of a bacterial exoenzyme.,Pautsch A, Vogelsgesang M, Trankle J, Herrmann C, Aktories K EMBO J. 2005 Oct 19;24(20):3670-80. Epub 2005 Sep 22. PMID:16177825<ref>PMID:16177825</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2a78" style="background-color:#fffaf0;"></div> | |||
== | ==See Also== | ||
*[[Exoenzyme 3D structures|Exoenzyme 3D structures]] | |||
[[Category: Clostridium botulinum | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Clostridium botulinum D phage]] | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Aktories | [[Category: Aktories K]] | ||
[[Category: Herrmann | [[Category: Herrmann C]] | ||
[[Category: Pautsch | [[Category: Pautsch A]] | ||
[[Category: Trankle | [[Category: Trankle J]] | ||
[[Category: Vogelsgesang | [[Category: Vogelsgesang M]] | ||