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| | ==CRYSTAL STRUCTURE OF PDE6D IN APO-STATE== | | ==CRYSTAL STRUCTURE OF PDE6D IN APO-STATE== |
| - | <StructureSection load='5t4x' size='340' side='right' caption='[[5t4x]], [[Resolution|resolution]] 1.81Å' scene=''> | + | <StructureSection load='5t4x' size='340' side='right'caption='[[5t4x]], [[Resolution|resolution]] 1.81Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5t4x]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5T4X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5T4X FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5t4x]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5T4X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5T4X FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Pde6d ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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]] 1.81Å</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=5t4x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5t4x OCA], [http://pdbe.org/5t4x PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5t4x RCSB], [http://www.ebi.ac.uk/pdbsum/5t4x PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5t4x ProSAT]</span></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=5t4x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5t4x OCA], [https://pdbe.org/5t4x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5t4x RCSB], [https://www.ebi.ac.uk/pdbsum/5t4x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5t4x ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PDE6D_MOUSE PDE6D_MOUSE]] Promotes the release of prenylated target proteins from cellular membranes (PubMed:22179043). Modulates the activity of prenylated or palmitoylated Ras family members by regulating their subcellular location (PubMed:22179043). Required for normal ciliary targeting of farnesylated target proteins, such as INPP5E (By similarity). Modulates the subcellular location of target proteins by acting as a GTP specific dissociation inhibitor (GDI) (PubMed:22179043). Increases the affinity of ARL3 for GTP by several orders of magnitude. Stabilizes ARL3-GTP by decreasing the nucleotide dissociation rate.[UniProtKB:O43924][UniProtKB:Q95142]<ref>PMID:10518933</ref> <ref>PMID:15979089</ref> <ref>PMID:22179043</ref> | + | [https://www.uniprot.org/uniprot/PDE6D_MOUSE PDE6D_MOUSE] Promotes the release of prenylated target proteins from cellular membranes (PubMed:22179043). Modulates the activity of prenylated or palmitoylated Ras family members by regulating their subcellular location (PubMed:22179043). Required for normal ciliary targeting of farnesylated target proteins, such as INPP5E (By similarity). Modulates the subcellular location of target proteins by acting as a GTP specific dissociation inhibitor (GDI) (PubMed:22179043). Increases the affinity of ARL3 for GTP by several orders of magnitude. Stabilizes ARL3-GTP by decreasing the nucleotide dissociation rate.[UniProtKB:O43924][UniProtKB:Q95142]<ref>PMID:10518933</ref> <ref>PMID:15979089</ref> <ref>PMID:22179043</ref> |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | Isoprenylated proteins are associated with membranes and their inter-compartmental distribution is regulated by solubilization factors, which incorporate lipid moieties in hydrophobic cavities and thereby facilitate free diffusion during trafficking. Here we report the crystal structure of a solubilization factor, the prenyl-binding protein (PrBP/delta), at 1.81 A resolution in its ligand-free apo-form. Apo-PrBP/delta harbors a preshaped, deep hydrophobic cavity, capacitating apo-PrBP/delta to readily bind its prenylated cargo. To investigate the molecular mechanism of cargo solubilization we analyzed the PrBP/delta-induced membrane dissociation of rod photoreceptor phosphodiesterase (PDE6). The results suggest that PrBP/delta exclusively interacts with the soluble fraction of PDE6. Depletion of soluble species in turn leads to dissociation of membrane-bound PDE6, as both are in equilibrium. This "solubilization by depletion" mechanism of PrBP/delta differs from the extraction of prenylated proteins by the similar folded solubilization factor RhoGDI, which interacts with membrane bound cargo via an N-terminal structural element lacking in PrBP/delta.
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| - | Mechanistic insights into the role of prenyl-binding protein PrBP/delta in membrane dissociation of phosphodiesterase 6.,Qureshi BM, Schmidt A, Behrmann E, Burger J, Mielke T, Spahn CMT, Heck M, Scheerer P Nat Commun. 2018 Jan 8;9(1):90. doi: 10.1038/s41467-017-02569-y. PMID:29311697<ref>PMID:29311697</ref>
| + | ==See Also== |
| - | | + | *[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]] |
| - | 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 5t4x" style="background-color:#fffaf0;"></div>
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| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Qureshi, B M]] | + | [[Category: Mus musculus]] |
| - | [[Category: Scheerer, P]] | + | [[Category: Qureshi BM]] |
| - | [[Category: Schmidt, A]] | + | [[Category: Scheerer P]] |
| - | [[Category: Apo-state]] | + | [[Category: Schmidt A]] |
| - | [[Category: Cellular trafficking]]
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| - | [[Category: Farnesyl]]
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| - | [[Category: Geranylgeranyl]]
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| - | [[Category: Immunoglobulin-like beta sandwitch]]
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| - | [[Category: Lipid binding protein]]
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| - | [[Category: Membrane dissociation]]
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| - | [[Category: Membrane trafficking]]
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| - | [[Category: Pde6 delta]]
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| - | [[Category: Phosphodiesterase 6]]
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| - | [[Category: Prenyl binding protein]]
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| - | [[Category: Ras-gtpase]]
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| - | [[Category: Rhodopsin]]
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| - | [[Category: Rhodopsin kinase]]
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| - | [[Category: Transport protein]]
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