|
|
| (One intermediate revision not shown.) |
| Line 1: |
Line 1: |
| | | | |
| | ==Structure of Fully modified farnesylated Rheb Peptide in complex with PDE6D== | | ==Structure of Fully modified farnesylated Rheb Peptide in complex with PDE6D== |
| - | <StructureSection load='3t5i' size='340' side='right' caption='[[3t5i]], [[Resolution|resolution]] 2.10Å' scene=''> | + | <StructureSection load='3t5i' size='340' side='right'caption='[[3t5i]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3t5i]] is a 6 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=3T5I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3T5I FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3t5i]] is a 6 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=3T5I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3T5I FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FAR:FARNESYL'>FAR</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]] 2.1Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CMT:O-METHYLCYSTEINE'>CMT</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CMT:O-METHYLCYSTEINE'>CMT</scene>, <scene name='pdbligand=FAR:FARNESYL'>FAR</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3t5g|3t5g]]</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=3t5i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3t5i OCA], [https://pdbe.org/3t5i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3t5i RCSB], [https://www.ebi.ac.uk/pdbsum/3t5i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3t5i ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PDE6D, PDED ([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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3t5i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3t5i OCA], [http://pdbe.org/3t5i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3t5i RCSB], [http://www.ebi.ac.uk/pdbsum/3t5i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3t5i ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PDE6D_HUMAN PDE6D_HUMAN]] Acts as a GTP specific dissociation inhibitor (GDI). Increases the affinity of ARL3 for GTP by several orders of magnitude and does so by decreasing the nucleotide dissociation rate. Stabilizes Arl3-GTP by decreasing the nucleotide dissociation (By similarity). | + | [https://www.uniprot.org/uniprot/PDE6D_HUMAN PDE6D_HUMAN] Acts as a GTP specific dissociation inhibitor (GDI). Increases the affinity of ARL3 for GTP by several orders of magnitude and does so by decreasing the nucleotide dissociation rate. Stabilizes Arl3-GTP by decreasing the nucleotide dissociation (By similarity). |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Lipidated Rho and Rab GTP-binding proteins are transported between membranes in complex with solubilizing factors called 'guanine nucleotide dissociation inhibitors' (GDIs). Unloading from GDIs using GDI displacement factors (GDFs) has been proposed but remains mechanistically elusive. PDEdelta is a putative solubilizing factor for several prenylated Ras-subfamily proteins. Here we report the structure of fully modified farnesylated Rheb-GDP in complex with PDEdelta. The structure explains the nucleotide-independent binding of Rheb to PDEdelta and the relaxed specificity of PDEdelta. We demonstrate that the G proteins Arl2 and Arl3 act in a GTP-dependent manner as allosteric release factors for farnesylated cargo. We thus describe a new transport system for farnesylated G proteins involving a GDI-like molecule and an unequivocal GDF. Considering the importance of PDEdelta for proper Ras and Rheb signaling, this study is instrumental in developing a new target for anticancer therapy.
| + | |
| | | | |
| - | Arl2-GTP and Arl3-GTP regulate a GDI-like transport system for farnesylated cargo.,Ismail SA, Chen YX, Rusinova A, Chandra A, Bierbaum M, Gremer L, Triola G, Waldmann H, Bastiaens PI, Wittinghofer A Nat Chem Biol. 2011 Oct 16. doi: 10.1038/nchembio.686. PMID:22002721<ref>PMID:22002721</ref>
| + | ==See Also== |
| - | | + | *[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]] |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 3t5i" style="background-color:#fffaf0;"></div>
| + | |
| - | == References == | + | |
| - | <references/>
| + | |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Chen, Y X]] | + | [[Category: Large Structures]] |
| - | [[Category: Ismail, S A]] | + | [[Category: Chen Y-X]] |
| - | [[Category: Wittinghofer, A]]
| + | [[Category: Ismail SA]] |
| - | [[Category: Farnesyl]]
| + | [[Category: Wittinghofer A]] |
| - | [[Category: Immunoglobulin-like beta sandwitch fold]]
| + | |
| - | [[Category: Lipid binding protein]] | + | |
| - | [[Category: Prenyl]] | + | |
| - | [[Category: Rheb]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
