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| | ==Crystal structure of the Grp1 PH domain in complex with Arf6-GTP== | | ==Crystal structure of the Grp1 PH domain in complex with Arf6-GTP== |
| - | <StructureSection load='4kax' size='340' side='right' caption='[[4kax]], [[Resolution|resolution]] 1.85Å' scene=''> | + | <StructureSection load='4kax' size='340' side='right'caption='[[4kax]], [[Resolution|resolution]] 1.85Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4kax]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KAX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4KAX FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4kax]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KAX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4KAX FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4IP:INOSITOL-(1,3,4,5)-TETRAKISPHOSPHATE'>4IP</scene>, <scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4IP:INOSITOL-(1,3,4,5)-TETRAKISPHOSPHATE'>4IP</scene>, <scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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]), CYTH3, ARNO3, GRP1, PSCD3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4kax FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kax OCA], [https://pdbe.org/4kax PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4kax RCSB], [https://www.ebi.ac.uk/pdbsum/4kax PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4kax ProSAT]</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=4kax FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kax OCA], [http://pdbe.org/4kax PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4kax RCSB], [http://www.ebi.ac.uk/pdbsum/4kax PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4kax 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/CYH3_HUMAN CYH3_HUMAN]] Promotes guanine-nucleotide exchange on ARF1. Promotes the activation of ARF through replacement of GDP with GTP. | + | [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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Berg, B van den]] | + | [[Category: Large Structures]] |
| - | [[Category: Lambright, D G]] | + | [[Category: Lambright DG]] |
| - | [[Category: Malaby, A W]] | + | [[Category: Malaby AW]] |
| - | [[Category: Ph domain]] | + | [[Category: Van den Berg B]] |
| - | [[Category: Phosphoinositide]]
| + | |
| - | [[Category: Protein binding-signaling protein complex]]
| + | |
| Structural highlights
4kax is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , , , , |
| 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]
Publication Abstract from PubMed
Membrane recruitment of cytohesin family Arf guanine nucleotide exchange factors depends on interactions with phosphoinositides and active Arf GTPases that, in turn, relieve autoinhibition of the catalytic Sec7 domain through an unknown structural mechanism. Here, we show that Arf6-GTP relieves autoinhibition by binding to an allosteric site that includes the autoinhibitory elements in addition to the PH domain. The crystal structure of a cytohesin-3 construct encompassing the allosteric site in complex with the head group of phosphatidyl inositol 3,4,5-trisphosphate and N-terminally truncated Arf6-GTP reveals a large conformational rearrangement, whereby autoinhibition can be relieved by competitive sequestration of the autoinhibitory elements in grooves at the Arf6/PH domain interface. Disposition of the known membrane targeting determinants on a common surface is compatible with multivalent membrane docking and subsequent activation of Arf substrates, suggesting a plausible model through which membrane recruitment and allosteric activation could be structurally integrated.
Structural basis for membrane recruitment and allosteric activation of cytohesin family Arf GTPase exchange factors.,Malaby AW, van den Berg B, Lambright DG Proc Natl Acad Sci U S A. 2013 Aug 12. PMID:23940353[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
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
- ↑ Malaby AW, van den Berg B, Lambright DG. Structural basis for membrane recruitment and allosteric activation of cytohesin family Arf GTPase exchange factors. Proc Natl Acad Sci U S A. 2013 Aug 12. PMID:23940353 doi:10.1073/pnas.1301883110
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