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| | ==Solution structure of RasGRP2 EF hands bound to calcium== | | ==Solution structure of RasGRP2 EF hands bound to calcium== |
| - | <StructureSection load='2ma2' size='340' side='right' caption='[[2ma2]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''> | + | <StructureSection load='2ma2' size='340' side='right'caption='[[2ma2]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2ma2]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MA2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2MA2 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2ma2]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MA2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MA2 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4l9m|4l9m]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RASGRP2, CDC25L, MCG7 ([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=2ma2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ma2 OCA], [https://pdbe.org/2ma2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ma2 RCSB], [https://www.ebi.ac.uk/pdbsum/2ma2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ma2 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=2ma2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ma2 OCA], [http://pdbe.org/2ma2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2ma2 RCSB], [http://www.ebi.ac.uk/pdbsum/2ma2 PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/GRP2_HUMAN GRP2_HUMAN]] Functions as a calcium- and DAG-regulated nucleotide exchange factor specifically activating Rap through the exchange of bound GDP for GTP. May also activates other GTPases such as RRAS, RRAS2, NRAS, KRAS but not HRAS. Functions in aggregation of platelets and adhesion of T-lymphocytes and neutrophils probably through inside-out integrin activation. May function in the muscarinic acetylcholine receptor M1/CHRM1 signaling pathway.<ref>PMID:10918068</ref> <ref>PMID:14702343</ref> <ref>PMID:17702895</ref> <ref>PMID:17576779</ref> | + | [https://www.uniprot.org/uniprot/GRP2_HUMAN GRP2_HUMAN] Functions as a calcium- and DAG-regulated nucleotide exchange factor specifically activating Rap through the exchange of bound GDP for GTP. May also activates other GTPases such as RRAS, RRAS2, NRAS, KRAS but not HRAS. Functions in aggregation of platelets and adhesion of T-lymphocytes and neutrophils probably through inside-out integrin activation. May function in the muscarinic acetylcholine receptor M1/CHRM1 signaling pathway.<ref>PMID:10918068</ref> <ref>PMID:14702343</ref> <ref>PMID:17702895</ref> <ref>PMID:17576779</ref> |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | RasGRP1 and SOS are Ras-specific nucleotide exchange factors that have distinct roles in lymphocyte development. RasGRP1 is important in some cancers and autoimmune diseases but, in contrast to SOS, its regulatory mechanisms are poorly understood. Activating signals lead to the membrane recruitment of RasGRP1 and Ras engagement, but it is unclear how interactions between RasGRP1 and Ras are suppressed in the absence of such signals. We present a crystal structure of a fragment of RasGRP1 in which the Ras-binding site is blocked by an interdomain linker and the membrane-interaction surface of RasGRP1 is hidden within a dimerization interface that may be stabilized by the C-terminal oligomerization domain. NMR data demonstrate that calcium binding to the regulatory module generates substantial conformational changes that are incompatible with the inactive assembly. These features allow RasGRP1 to be maintained in an inactive state that is poised for activation by calcium and membrane-localization signals. DOI:http://dx.doi.org/10.7554/eLife.00813.001.
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| - | Structural analysis of autoinhibition in the Ras-specific exchange factor RasGRP1.,Iwig JS, Vercoulen Y, Das R, Barros T, Limnander A, Che Y, Pelton JG, Wemmer DE, Roose JP, Kuriyan J Elife. 2013 Jul 30;2:e00813. doi: 10.7554/eLife.00813. Print 2013. PMID:23908768<ref>PMID:23908768</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 2ma2" style="background-color:#fffaf0;"></div>
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| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Barros, T]] | + | [[Category: Large Structures]] |
| - | [[Category: Che, Y]] | + | [[Category: Barros T]] |
| - | [[Category: Das, R]] | + | [[Category: Che Y]] |
| - | [[Category: Iwig, J]] | + | [[Category: Das R]] |
| - | [[Category: Kuriyan, J]] | + | [[Category: Iwig J]] |
| - | [[Category: Limnander, A]] | + | [[Category: Kuriyan J]] |
| - | [[Category: Pelton, J]] | + | [[Category: Limnander A]] |
| - | [[Category: Roose, J]] | + | [[Category: Pelton J]] |
| - | [[Category: Vercoulen, Y]] | + | [[Category: Roose J]] |
| - | [[Category: Wemmer, D]] | + | [[Category: Vercoulen Y]] |
| - | [[Category: Calcium-binding protein]]
| + | [[Category: Wemmer D]] |
| - | [[Category: Ef hand]]
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| - | [[Category: Protein]]
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| Structural highlights
Function
GRP2_HUMAN Functions as a calcium- and DAG-regulated nucleotide exchange factor specifically activating Rap through the exchange of bound GDP for GTP. May also activates other GTPases such as RRAS, RRAS2, NRAS, KRAS but not HRAS. Functions in aggregation of platelets and adhesion of T-lymphocytes and neutrophils probably through inside-out integrin activation. May function in the muscarinic acetylcholine receptor M1/CHRM1 signaling pathway.[1] [2] [3] [4]
References
- ↑ Clyde-Smith J, Silins G, Gartside M, Grimmond S, Etheridge M, Apolloni A, Hayward N, Hancock JF. Characterization of RasGRP2, a plasma membrane-targeted, dual specificity Ras/Rap exchange factor. J Biol Chem. 2000 Oct 13;275(41):32260-7. PMID:10918068 doi:10.1074/jbc.M006087200
- ↑ Katagiri K, Shimonaka M, Kinashi T. Rap1-mediated lymphocyte function-associated antigen-1 activation by the T cell antigen receptor is dependent on phospholipase C-gamma1. J Biol Chem. 2004 Mar 19;279(12):11875-81. Epub 2003 Dec 31. PMID:14702343 doi:10.1074/jbc.M310717200
- ↑ Ghandour H, Cullere X, Alvarez A, Luscinskas FW, Mayadas TN. Essential role for Rap1 GTPase and its guanine exchange factor CalDAG-GEFI in LFA-1 but not VLA-4 integrin mediated human T-cell adhesion. Blood. 2007 Nov 15;110(10):3682-90. Epub 2007 Aug 16. PMID:17702895 doi:blood-2007-03-077628
- ↑ Pasvolsky R, Feigelson SW, Kilic SS, Simon AJ, Tal-Lapidot G, Grabovsky V, Crittenden JR, Amariglio N, Safran M, Graybiel AM, Rechavi G, Ben-Dor S, Etzioni A, Alon R. A LAD-III syndrome is associated with defective expression of the Rap-1 activator CalDAG-GEFI in lymphocytes, neutrophils, and platelets. J Exp Med. 2007 Jul 9;204(7):1571-82. Epub 2007 Jun 18. PMID:17576779 doi:10.1084/jem.20070058
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