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| ==Structure of autoinhibited P-Rex1== | | ==Structure of autoinhibited P-Rex1== |
| <StructureSection load='7rx9' size='340' side='right'caption='[[7rx9]], [[Resolution|resolution]] 3.22Å' scene=''> | | <StructureSection load='7rx9' size='340' side='right'caption='[[7rx9]]' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[7rx9]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RX9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RX9 FirstGlance]. <br> | | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RX9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RX9 FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=7rx9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rx9 OCA], [https://pdbe.org/7rx9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rx9 RCSB], [https://www.ebi.ac.uk/pdbsum/7rx9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rx9 ProSAT]</span></td></tr> |
| <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Lysozyme Lysozyme], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.17 3.2.1.17] </span></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=7rx9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rx9 OCA], [https://pdbe.org/7rx9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rx9 RCSB], [https://www.ebi.ac.uk/pdbsum/7rx9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rx9 ProSAT]</span></td></tr> | |
| </table> | | </table> |
| == Function ==
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| [[https://www.uniprot.org/uniprot/PREX1_HUMAN PREX1_HUMAN]] Functions as a RAC guanine nucleotide exchange factor (GEF), which activates the Rac proteins by exchanging bound GDP for free GTP. Its activity is synergistically activated by phosphatidylinositol 3,4,5-trisphosphate and the beta gamma subunits of heterotrimeric G protein. May function downstream of heterotrimeric G proteins in neutrophils.
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| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| P-Rex (PI(3,4,5)P3-dependent Rac exchanger) guanine nucleotide exchange factors potently activate Rho GTPases. P-Rex guanine nucleotide exchange factors are autoinhibited, synergistically activated by Gbetagamma and PI(3,4,5)P3 binding and dysregulated in cancer. Here, we use X-ray crystallography, cryogenic electron microscopy and crosslinking mass spectrometry to determine the structural basis of human P-Rex1 autoinhibition. P-Rex1 has a bipartite structure of N- and C-terminal modules connected by a C-terminal four-helix bundle that binds the N-terminal Pleckstrin homology (PH) domain. In the N-terminal module, the Dbl homology (DH) domain catalytic surface is occluded by the compact arrangement of the DH-PH-DEP1 domains. Structural analysis reveals a remarkable conformational transition to release autoinhibition, requiring a 126 degrees opening of the DH domain hinge helix. The off-axis position of Gbetagamma and PI(3,4,5)P3 binding sites further suggests a counter-rotation of the P-Rex1 halves by 90 degrees facilitates PH domain uncoupling from the four-helix bundle, releasing the autoinhibited DH domain to drive Rho GTPase signaling.
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| Structure of the metastatic factor P-Rex1 reveals a two-layered autoinhibitory mechanism.,Chang YG, Lupton CJ, Bayly-Jones C, Keen AC, D'Andrea L, Lucato CM, Steele JR, Venugopal H, Schittenhelm RB, Whisstock JC, Halls ML, Ellisdon AM Nat Struct Mol Biol. 2022 Jul 21. pii: 10.1038/s41594-022-00804-9. doi:, 10.1038/s41594-022-00804-9. PMID:35864164<ref>PMID:35864164</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 7rx9" style="background-color:#fffaf0;"></div>
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| == References ==
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| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Lysozyme]]
| | [[Category: Chang Y]] |
| [[Category: Chang, Y]] | | [[Category: Ellisdon AM]] |
| [[Category: Ellisdon, A M]] | |
| [[Category: Cdc42]]
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| [[Category: Cell growth]]
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| [[Category: Gef]]
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| [[Category: P-rex1]]
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| [[Category: P-rex2]]
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| [[Category: Rac1]]
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| [[Category: Signaling protein]]
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