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| | ==Cholera toxin A1 subunit bound to its substrate, NAD+, and its human protein activator, ARF6== | | ==Cholera toxin A1 subunit bound to its substrate, NAD+, and its human protein activator, ARF6== |
| - | <StructureSection load='2a5f' size='340' side='right' caption='[[2a5f]], [[Resolution|resolution]] 2.02Å' scene=''> | + | <StructureSection load='2a5f' size='340' side='right'caption='[[2a5f]], [[Resolution|resolution]] 2.02Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2a5f]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillo_virgola_del_koch"_trevisan_1884 "bacillo virgola del koch" trevisan 1884] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2A5F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2A5F FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2a5f]] 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=2A5F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2A5F FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr> | + | </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>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ARF6 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), ctxA, toxA ([http://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='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'>[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] </span></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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2a5f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2a5f OCA], [http://pdbe.org/2a5f PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2a5f RCSB], [http://www.ebi.ac.uk/pdbsum/2a5f PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2a5f 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=2a5f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2a5f OCA], [https://pdbe.org/2a5f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2a5f RCSB], [https://www.ebi.ac.uk/pdbsum/2a5f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2a5f ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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> [[http://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. | + | [[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 == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | ==See Also== | | ==See Also== |
| - | *[[Cholera toxin|Cholera toxin]] | + | *[[Cholera toxin 3D structures|Cholera toxin 3D structures]] |
| | *[[User:David Solfiell/sandbox 1|User:David Solfiell/sandbox 1]] | | *[[User:David Solfiell/sandbox 1|User:David Solfiell/sandbox 1]] |
| | == References == | | == References == |
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| | [[Category: Bacillo virgola del koch trevisan 1884]] | | [[Category: Bacillo virgola del koch trevisan 1884]] |
| | [[Category: Human]] | | [[Category: Human]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Hol, W G.J]] | | [[Category: Hol, W G.J]] |
| | [[Category: Holmes, R K]] | | [[Category: Holmes, R K]] |
| Structural highlights
2a5f is a 2 chain structure with sequence from "bacillo_virgola_del_koch"_trevisan_1884 "bacillo virgola del koch" trevisan 1884 and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , , , |
| Gene: | ARF6 (HUMAN), ctxA, toxA ("Bacillo virgola del Koch" Trevisan 1884) |
| Activity: | NAD(+)--diphthamide ADP-ribosyltransferase, with EC number 2.4.2.36 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[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.[1] [2] [3] [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
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 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[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ D'Souza-Schorey C, Stahl PD. Myristoylation is required for the intracellular localization and endocytic function of ARF6. Exp Cell Res. 1995 Nov;221(1):153-9. PMID:7589240 doi:http://dx.doi.org/10.1006/excr.1995.1362
- ↑ Gauthier-Campbell C, Bredt DS, Murphy TH, El-Husseini Ael-D. Regulation of dendritic branching and filopodia formation in hippocampal neurons by specific acylated protein motifs. Mol Biol Cell. 2004 May;15(5):2205-17. Epub 2004 Feb 20. PMID:14978216 doi:10.1091/mbc.E03-07-0493
- ↑ Pasqualato S, Menetrey J, Franco M, Cherfils J. The structural GDP/GTP cycle of human Arf6. EMBO Rep. 2001 Mar;2(3):234-8. PMID:11266366 doi:10.1093/embo-reports/kve043
- ↑ O'Neal CJ, Jobling MG, Holmes RK, Hol WG. Structural basis for the activation of cholera toxin by human ARF6-GTP. Science. 2005 Aug 12;309(5737):1093-6. PMID:16099990 doi:309/5737/1093
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