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New page: left|200px<br /> <applet load="2a5d" size="450" color="white" frame="true" align="right" spinBox="true" caption="2a5d, resolution 1.80Å" /> '''Structural basis fo...
 
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[[Image:2a5d.gif|left|200px]]<br />
<applet load="2a5d" size="450" color="white" frame="true" align="right" spinBox="true"
caption="2a5d, resolution 1.80&Aring;" />
'''Structural basis for the activation of cholera toxin by human ARF6-GTP'''<br />


==Overview==
==Structural basis for the activation of cholera toxin by human ARF6-GTP==
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.
<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/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Vibrio_cholerae Vibrio cholerae]. 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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</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='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>
== 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].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== 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.


==About this Structure==
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>
2A5D is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Vibrio_cholerae Vibrio cholerae] with NA, MG, GTP and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/NAD(+)--diphthamide_ADP-ribosyltransferase NAD(+)--diphthamide ADP-ribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.36 2.4.2.36] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2A5D OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16099990 16099990]
</div>
<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: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: NAD(+)--diphthamide ADP-ribosyltransferase]]
[[Category: Large Structures]]
[[Category: Protein complex]]
[[Category: Vibrio cholerae]]
[[Category: Vibrio cholerae]]
[[Category: Hol, W.G.J.]]
[[Category: Hol WGJ]]
[[Category: Holmes, R.K.]]
[[Category: Holmes RK]]
[[Category: Jobling, M.G.]]
[[Category: Jobling MG]]
[[Category: Neal, C.J.O.]]
[[Category: O'Neal CJ]]
[[Category: GOL]]
[[Category: GTP]]
[[Category: MG]]
[[Category: NA]]
[[Category: protein transport/transferase]]
 
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