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| ==The C2A domain of Rabphilin 3A in complex with PI(4,5)P2== | | ==The C2A domain of Rabphilin 3A in complex with PI(4,5)P2== |
| <StructureSection load='4ns0' size='340' side='right'caption='[[4ns0]], [[Resolution|resolution]] 1.80Å' scene=''> | | <StructureSection load='4ns0' size='340' side='right'caption='[[4ns0]]' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[4ns0]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NS0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NS0 FirstGlance]. <br> | | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NS0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NS0 FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PIO:[(2R)-2-OCTANOYLOXY-3-[OXIDANYL-[(1R,2R,3S,4R,5R,6S)-2,3,6-TRIS(OXIDANYL)-4,5-DIPHOSPHONOOXY-CYCLOHEXYL]OXY-PHOSPHORYL]OXY-PROPYL]+OCTANOATE'>PIO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | | </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=4ns0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ns0 OCA], [https://pdbe.org/4ns0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ns0 RCSB], [https://www.ebi.ac.uk/pdbsum/4ns0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ns0 ProSAT]</span></td></tr> |
| <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[4np9|4np9]], [[4lt7|4lt7]]</div></td></tr>
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| <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4ns0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ns0 OCA], [https://pdbe.org/4ns0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ns0 RCSB], [https://www.ebi.ac.uk/pdbsum/4ns0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ns0 ProSAT]</span></td></tr> | |
| </table> | | </table> |
| == Function ==
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| [[https://www.uniprot.org/uniprot/RP3A_RAT RP3A_RAT]] Protein transport. Probably involved with Ras-related protein Rab-3A in synaptic vesicle traffic and/or synaptic vesicle fusion. Could play a role in neurotransmitter release by regulating membrane flow in the nerve terminal.
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| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| Proteins containing C2 domains are the sensors for Ca(2+) and PI(4,5)P2 in a myriad of secretory pathways. Here, the use of a free-mounting system has enabled us to capture an intermediate state of Ca(2+) binding to the C2A domain of rabphilin 3A that suggests a different mechanism of ion interaction. We have also determined the structure of this domain in complex with PI(4,5)P2 and IP3 at resolutions of 1.75 and 1.9 A, respectively, unveiling that the polybasic cluster formed by strands beta3-beta4 is involved in the interaction with the phosphoinositides. A comparative study demonstrates that the C2A domain is highly specific for PI(4,5)P2/PI(3,4,5)P3, whereas the C2B domain cannot discriminate among any of the diphosphorylated forms. Structural comparisons between C2A domains of rabphilin 3A and synaptotagmin 1 indicated the presence of a key glutamic residue in the polybasic cluster of synaptotagmin 1 that abolishes the interaction with PI(4,5)P2. Together, these results provide a structural explanation for the ability of different C2 domains to pull plasma and vesicle membranes close together in a Ca(2+)-dependent manner and reveal how this family of proteins can use subtle structural changes to modulate their sensitivity and specificity to various cellular signals.
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| Structural insights into the Ca2+ and PI(4,5)P2 binding modes of the C2 domains of rabphilin 3A and synaptotagmin 1.,Guillen J, Ferrer-Orta C, Buxaderas M, Perez-Sanchez D, Guerrero-Valero M, Luengo-Gil G, Pous J, Guerra P, Gomez-Fernandez JC, Verdaguer N, Corbalan-Garcia S Proc Natl Acad Sci U S A. 2013 Dec 17;110(51):20503-8. doi:, 10.1073/pnas.1316179110. Epub 2013 Dec 3. PMID:24302762<ref>PMID:24302762</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 4ns0" style="background-color:#fffaf0;"></div>
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| ==See Also== | | ==See Also== |
| *[[Exophilin 3D structures|Exophilin 3D structures]] | | *[[Exophilin 3D structures|Exophilin 3D structures]] |
| *[[Rabphilin|Rabphilin]] | | *[[Rabphilin|Rabphilin]] |
| == References ==
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| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Buxaderas, M]] | | [[Category: Buxaderas M]] |
| [[Category: Corbalan-Garcia, S]] | | [[Category: Corbalan-Garcia S]] |
| [[Category: Ferrer-Orta, C]] | | [[Category: Ferrer-Orta C]] |
| [[Category: Gomez-Fernandez, J C]] | | [[Category: Gomez-Fernandez JC]] |
| [[Category: Guerra, P]] | | [[Category: Guerra P]] |
| [[Category: Guerrero-Valero, M]] | | [[Category: Guerrero-Valero M]] |
| [[Category: Guillen, J]] | | [[Category: Guillen J]] |
| [[Category: Luengo-Gil, G]] | | [[Category: Luengo-Gil G]] |
| [[Category: Perez-sanchez, D]] | | [[Category: Perez-sanchez D]] |
| [[Category: Pous, J]] | | [[Category: Pous J]] |
| [[Category: Verdaguer, N]] | | [[Category: Verdaguer N]] |
| [[Category: C-2 domain fold]]
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| [[Category: C2 domain]]
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| [[Category: C2a]]
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| [[Category: Calcium binding]]
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| [[Category: Exophilin-1]]
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| [[Category: Phospholipid binding]]
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| [[Category: Protein transport]]
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| [[Category: Rabphilin-3a]]
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| [[Category: Synaptic exocytosis metal-binding]]
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