View source for 2a5d


==Structural basis for the activation of cholera toxin by human ARF6-GTP==
<StructureSection load='2a5d' size='340' side='right'caption='[[2a5d]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2a5d]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillo_virgola_del_koch"_trevisan_1884 "bacillo virgola del koch" trevisan 1884] and [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2A5D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2A5D FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2a5f|2a5f]], [[2a5g|2a5g]]</div></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ARF6 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), ctxA, toxA ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=666 "Bacillo virgola del Koch" Trevisan 1884])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/NAD(+)--diphthamide_ADP-ribosyltransferase NAD(+)--diphthamide ADP-ribosyltransferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.36 2.4.2.36] </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=2a5d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2a5d OCA], [https://pdbe.org/2a5d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2a5d RCSB], [https://www.ebi.ac.uk/pdbsum/2a5d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2a5d ProSAT]</span></td></tr>
</table>
== Function ==
[[https://www.uniprot.org/uniprot/ARF6_HUMAN ARF6_HUMAN]] GTP-binding protein involved in protein trafficking; regulates endocytic recycling and cytoskeleton remodeling. May modulate vesicle budding and uncoating within the Golgi apparatus. Functions as an allosteric activator of the cholera toxin catalytic subunit, an ADP-ribosyltransferase. Involved in the regulation of dendritic spine development (By similarity). Contributes to the regulation of dendritic branching and filopodia extension.<ref>PMID:7589240</ref> <ref>PMID:14978216</ref> <ref>PMID:11266366</ref>  [[https://www.uniprot.org/uniprot/CHTA_VIBCH CHTA_VIBCH]] The A1 chain catalyzes the ADP-ribosylation of Gs alpha, a GTP-binding regulatory protein, to activate the adenylate cyclase. This leads to an overproduction of cAMP and eventually to a hypersecretion of chloride and bicarbonate followed by water, resulting in the characteristic cholera stool. The A2 chain tethers A1 to the pentameric ring. 
== 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/a5/2a5d_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=2a5d ConSurf].
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== Publication Abstract from PubMed ==
The Vibrio cholerae bacterium causes devastating diarrhea when it infects the human intestine. The key event is adenosine diphosphate (ADP)-ribosylation of the human signaling protein GSalpha, catalyzed by the cholera toxin A1 subunit (CTA1). This reaction is allosterically activated by human ADP-ribosylation factors (ARFs), a family of essential and ubiquitous G proteins. Crystal structures of a CTA1:ARF6-GTP (guanosine triphosphate) complex reveal that binding of the human activator elicits dramatic changes in CTA1 loop regions that allow nicotinamide adenine dinucleotide (NAD+) to bind to the active site. The extensive toxin:ARF-GTP interface surface mimics ARF-GTP recognition of normal cellular protein partners, which suggests that the toxin has evolved to exploit promiscuous binding properties of ARFs.

Structural basis for the activation of cholera toxin by human ARF6-GTP.,O'Neal CJ, Jobling MG, Holmes RK, Hol WG Science. 2005 Aug 12;309(5737):1093-6. PMID:16099990<ref>PMID:16099990</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 2a5d" style="background-color:#fffaf0;"></div>

==See Also==
*[[Cholera toxin 3D structures|Cholera toxin 3D structures]]
*[[User:David Solfiell/sandbox 1|User:David Solfiell/sandbox 1]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bacillo virgola del koch trevisan 1884]]
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Hol, W G.J]]
[[Category: Holmes, R K]]
[[Category: Jobling, M G]]
[[Category: Neal, C J.O]]
[[Category: Protein transport-transferase complex]]
[[Category: Protein transport/transferase]]