View source for 5fi1


==Crystal Structure of the P-Rex1 DH/PH tandem in complex with Cdc42==
<StructureSection load='5fi1' size='340' side='right'caption='[[5fi1]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5fi1]] 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=5FI1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5FI1 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.203&#8491;</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=5fi1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fi1 OCA], [https://pdbe.org/5fi1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5fi1 RCSB], [https://www.ebi.ac.uk/pdbsum/5fi1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5fi1 ProSAT]</span></td></tr>
</table>
== Function ==
[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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== Publication Abstract from PubMed ==
Phosphatidylinositol 3,4,5-trisphosphate (PIP3)-dependent Rac exchanger 1 (P-Rex1) is a Rho guanine nucleotide exchange factor synergistically activated by PIP3 and Gbetagamma that plays an important role in the metastasis of breast, prostate, and skin cancer, making it an attractive therapeutic target. However, the molecular mechanisms behind P-Rex1 regulation are poorly understood. We determined structures of the P-Rex1 pleckstrin homology (PH) domain bound to the headgroup of PIP3 and resolved that PIP3 binding to the PH domain is required for P-Rex1 activity in cells but not for membrane localization, which points to an allosteric activation mechanism by PIP3. We also determined structures of the P-Rex1 tandem Dbl homology/PH domains in complexes with two of its substrate GTPases, Rac1 and Cdc42. Collectively, this study provides important molecular insights into P-Rex1 regulation and tools for targeting the PIP3-binding pocket of P-Rex1 with a new generation of cancer chemotherapeutic agents.

Structural and Biochemical Characterization of the Catalytic Core of the Metastatic Factor P-Rex1 and Its Regulation by PtdIns(3,4,5)P3.,Cash JN, Davis EM, Tesmer JJ Structure. 2016 May 3;24(5):730-40. doi: 10.1016/j.str.2016.02.022. Epub 2016 Apr, 14. PMID:27150042<ref>PMID:27150042</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5fi1" style="background-color:#fffaf0;"></div>

==See Also==
*[[GTP-binding protein 3D structures|GTP-binding protein 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Cash JN]]
[[Category: Tesmer JJG]]