6c1z | pdb_00006c1z
Crystal structure of Apo Caenorhabditis elegans lipid binding protein 8 (LBP-8)
Structural highlights
FunctionFABP8_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 PubMedThe 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
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