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| | ==The crystal structure of ASAP3 in complex with Arf6 in transition state== | | ==The crystal structure of ASAP3 in complex with Arf6 in transition state== |
| - | <StructureSection load='3lvq' size='340' side='right' caption='[[3lvq]], [[Resolution|resolution]] 3.38Å' scene=''> | + | <StructureSection load='3lvq' size='340' side='right'caption='[[3lvq]], [[Resolution|resolution]] 3.38Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3lvq]] is a 1 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=3LVQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3LVQ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3lvq]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LVQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3LVQ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AF3:ALUMINUM+FLUORIDE'>AF3</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.38Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3lvr|3lvr]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AF3:ALUMINUM+FLUORIDE'>AF3</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ASAP3, ARF6 ([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=3lvq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lvq OCA], [https://pdbe.org/3lvq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3lvq RCSB], [https://www.ebi.ac.uk/pdbsum/3lvq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3lvq 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=3lvq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lvq OCA], [http://pdbe.org/3lvq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3lvq RCSB], [http://www.ebi.ac.uk/pdbsum/3lvq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3lvq ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ASAP3_HUMAN ASAP3_HUMAN]] Promotes cell proliferation.<ref>PMID:14654939</ref> | + | [https://www.uniprot.org/uniprot/ASAP3_HUMAN ASAP3_HUMAN] Promotes cell proliferation.<ref>PMID:14654939</ref> [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 == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Ismail, S A]] | + | [[Category: Large Structures]] |
| - | [[Category: Sot, B]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Vetter, I R]] | + | [[Category: Ismail SA]] |
| - | [[Category: Wittinghofer, A]] | + | [[Category: Sot B]] |
| - | [[Category: Alternative splicing]] | + | [[Category: Vetter IR]] |
| - | [[Category: Ank repeat]] | + | [[Category: Wittinghofer A]] |
| - | [[Category: Arf]]
| + | |
| - | [[Category: Arf6]]
| + | |
| - | [[Category: Arfgap]]
| + | |
| - | [[Category: Asap3]]
| + | |
| - | [[Category: Cell membrane]]
| + | |
| - | [[Category: Coiled coil]]
| + | |
| - | [[Category: Cytoplasm]]
| + | |
| - | [[Category: Endosome]]
| + | |
| - | [[Category: Er-golgi transport]]
| + | |
| - | [[Category: Gap]]
| + | |
| - | [[Category: Gdp]]
| + | |
| - | [[Category: Golgi apparatus]]
| + | |
| - | [[Category: Gtp-binding]]
| + | |
| - | [[Category: Linker]]
| + | |
| - | [[Category: Lipoprotein]]
| + | |
| - | [[Category: Metal-binding]]
| + | |
| - | [[Category: Myristate]]
| + | |
| - | [[Category: Nucleotide-binding]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| - | [[Category: Polymorphism]]
| + | |
| - | [[Category: Protein transport]]
| + | |
| - | [[Category: Transport]]
| + | |
| - | [[Category: Uplc1]]
| + | |
| - | [[Category: Zinc]]
| + | |
| - | [[Category: Zinc-finger]]
| + | |
| Structural highlights
Function
ASAP3_HUMAN Promotes cell proliferation.[1] 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.[2] [3] [4]
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
Arfs are small G proteins that have a key role in vesicle trafficking and cytoskeletal remodeling. ArfGAP proteins stimulate Arf intrinsic GTP hydrolysis by a mechanism that is still unresolved. Using a fusion construct we solved the structure of the ArfGAP ASAP3 in complex with Arf6 in the transition state. This structure clarifies the ArfGAP catalytic mechanism and shows a glutamine((Arf6)) and an arginine finger((ASAP3)) as the important catalytic residues. Unexpectedly the structure shows a calcium ion, liganded by both proteins in the complex interface, stabilizing the interaction and orienting the catalytic machinery. Calcium stimulates the GAP activity of ASAPs, but not other members of the ArfGAP family. This type of regulation is unique for GAPs and any other calcium-regulated processes and hints at a crosstalk between Ca(2+) and Arf signaling.
The structure of an Arf-ArfGAP complex reveals a Ca2+ regulatory mechanism.,Ismail SA, Vetter IR, Sot B, Wittinghofer A Cell. 2010 May 28;141(5):812-21. PMID:20510928[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Okabe H, Furukawa Y, Kato T, Hasegawa S, Yamaoka Y, Nakamura Y. Isolation of development and differentiation enhancing factor-like 1 (DDEFL1) as a drug target for hepatocellular carcinomas. Int J Oncol. 2004 Jan;24(1):43-8. PMID:14654939
- ↑ 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
- ↑ Ismail SA, Vetter IR, Sot B, Wittinghofer A. The structure of an Arf-ArfGAP complex reveals a Ca2+ regulatory mechanism. Cell. 2010 May 28;141(5):812-21. PMID:20510928 doi:10.1016/j.cell.2010.03.051
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