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| | <StructureSection load='6c1z' size='340' side='right'caption='[[6c1z]], [[Resolution|resolution]] 1.30Å' scene=''> | | <StructureSection load='6c1z' size='340' side='right'caption='[[6c1z]], [[Resolution|resolution]] 1.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6c1z]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Caeel Caeel]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6C1Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6C1Z FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6c1z]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Caenorhabditis_elegans Caenorhabditis elegans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6C1Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6C1Z FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.3Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">lbp-8, CELE_T22G5.6, T22G5.6 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=6239 CAEEL])</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> |
| - | <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=6c1z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6c1z OCA], [http://pdbe.org/6c1z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6c1z RCSB], [http://www.ebi.ac.uk/pdbsum/6c1z PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6c1z 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=6c1z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6c1z OCA], [https://pdbe.org/6c1z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6c1z RCSB], [https://www.ebi.ac.uk/pdbsum/6c1z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6c1z ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/FABP8_CAEEL FABP8_CAEEL] Lysosomal lipid chaperone which binds to a wide range of unsaturated fatty acids, including high affinity binding to oleic acid and oleoylethanolamide, to transport them into the nucleus (PubMed:31292465, PubMed:25554789). As part of a lysosome-to-nucleus retrograde lipid signaling pathway, translocates into the nucleus where it activates the transcription of genes promoting longevity and activation of mitochondrial beta oxidation (PubMed:30713071, PubMed:25554789).<ref>PMID:25554789</ref> <ref>PMID:30713071</ref> <ref>PMID:31292465</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Caeel]] | + | [[Category: Caenorhabditis elegans]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Ortlund, E A]] | + | [[Category: Ortlund EA]] |
| - | [[Category: Tillman, M C]] | + | [[Category: Tillman MC]] |
| - | [[Category: Aging]]
| + | |
| - | [[Category: C. elegan]]
| + | |
| - | [[Category: Caenorhabditis elegan]]
| + | |
| - | [[Category: Fabp]]
| + | |
| - | [[Category: Fatty acid]]
| + | |
| - | [[Category: Fatty acid binding protein]]
| + | |
| - | [[Category: Lbp-8]]
| + | |
| - | [[Category: Lbp8]]
| + | |
| - | [[Category: Lipid]]
| + | |
| - | [[Category: Lipid binding protein]]
| + | |
| - | [[Category: Lipid binding protein 8]]
| + | |
| - | [[Category: Lipid transport]]
| + | |
| - | [[Category: Lysosome]]
| + | |
| - | [[Category: Monounsaturated fatty acid]]
| + | |
| Structural highlights
Function
FABP8_CAEEL Lysosomal lipid chaperone which binds to a wide range of unsaturated fatty acids, including high affinity binding to oleic acid and oleoylethanolamide, to transport them into the nucleus (PubMed:31292465, PubMed:25554789). As part of a lysosome-to-nucleus retrograde lipid signaling pathway, translocates into the nucleus where it activates the transcription of genes promoting longevity and activation of mitochondrial beta oxidation (PubMed:30713071, PubMed:25554789).[1] [2] [3]
Publication Abstract from PubMed
The lysosome plays a crucial role in the regulation of longevity. Lysosomal degradation is tightly coupled with autophagy that is induced by many longevity paradigms and required for lifespan extension. The lysosome also serves as a hub for signal transduction and regulates longevity via affecting nuclear transcription. One lysosome-to-nucleus retrograde signaling pathway is mediated by a lysosome-associated fatty acid binding protein LBP-8 in Caenorhabditis elegans. LBP-8 shuttles lysosomal lipids into the nucleus to activate lipid regulated nuclear receptors NHR-49 and NHR-80 and consequently promote longevity. However, the structural basis of LBP-8 action remains unclear. Here, we determined the first 1.3 A high-resolution structure of this life-extending protein LBP-8, which allowed us to identify a structurally conserved nuclear localization signal and amino acids involved in lipid binding. Additionally, we described the range of fatty acids LBP-8 is capable of binding and show that it binds to life-extending ligands in worms such as oleic acid and oleoylethanolamide with high affinity.
Structural characterization of life-extending Caenorhabditis elegans Lipid Binding Protein 8.,Tillman MC, Khadka M, Duffy J, Wang MC, Ortlund EA Sci Rep. 2019 Jul 10;9(1):9966. doi: 10.1038/s41598-019-46230-8. PMID:31292465[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Folick A, Oakley HD, Yu Y, Armstrong EH, Kumari M, Sanor L, Moore DD, Ortlund EA, Zechner R, Wang MC. Aging. Lysosomal signaling molecules regulate longevity in Caenorhabditis elegans. Science. 2015 Jan 2;347(6217):83-6. PMID:25554789 doi:10.1126/science.1258857
- ↑ Ramachandran PV, Savini M, Folick AK, Hu K, Masand R, Graham BH, Wang MC. Lysosomal Signaling Promotes Longevity by Adjusting Mitochondrial Activity. Dev Cell. 2019 Mar 11;48(5):685-696.e5. PMID:30713071 doi:10.1016/j.devcel.2018.12.022
- ↑ Tillman MC, Khadka M, Duffy J, Wang MC, Ortlund EA. Structural characterization of life-extending Caenorhabditis elegans Lipid Binding Protein 8. Sci Rep. 2019 Jul 10;9(1):9966. doi: 10.1038/s41598-019-46230-8. PMID:31292465 doi:http://dx.doi.org/10.1038/s41598-019-46230-8
- ↑ Tillman MC, Khadka M, Duffy J, Wang MC, Ortlund EA. Structural characterization of life-extending Caenorhabditis elegans Lipid Binding Protein 8. Sci Rep. 2019 Jul 10;9(1):9966. doi: 10.1038/s41598-019-46230-8. PMID:31292465 doi:http://dx.doi.org/10.1038/s41598-019-46230-8
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