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.

Abstract

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 Å 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / chemistry*
  • Cell Nucleus / metabolism*
  • Fatty Acid-Binding Proteins / metabolism
  • Fatty Acids / metabolism*
  • Helix-Turn-Helix Motifs
  • Longevity / physiology*
  • Lysosomes / metabolism*
  • Molecular Chaperones / chemistry*

Substances

  • Caenorhabditis elegans Proteins
  • Fatty Acid-Binding Proteins
  • Fatty Acids
  • LBP-8 protein, C elegans
  • Molecular Chaperones