9dxi
Crystal structure of dimer Caenorhabditis elegans lipid binding protein 3 (LBP-3)
Structural highlights
FunctionFABP3_CAEEL May play a role in sequestering potentially toxic fatty acids and their peroxidation products, or it may be involved in the maintenance of the impermeable lipid layer of the eggshell.[1] Publication Abstract from PubMedIntracellular lipid binding proteins (iLBPs) play crucial roles in lipid transport and cellular metabolism across the animal kingdom. Recently, a fat-to-neuron axis was described in Caenorhabditis elegans, in which lysosomal activity in the fat liberates polyunsaturated fatty acids (PUFAs) that signal to neurons and extend lifespan with durable fecundity. In this study, we investigate the structure and binding mechanisms of a lifespan-extending lipid chaperone, lipid binding protein-3 (LBP-3), which shuttles dihomo-gamma-linolenic (DGLA) acid from intestinal fat to neurons. We present the first high-resolution crystal structure of LBP-3, which reveals a classic iLBP fold with an unexpected and unique homodimeric arrangement via interstrand interactions that is incompatible with ligand binding. We identify key ionic interactions that mediate DGLA binding within the lipid binding pocket. Molecular dynamics simulations further elucidate LBP-3's preferential binding to DGLA due to its rotational freedom and access to favorable binding conformations compared to other 20-carbon PUFAs. We also propose that LBP-3 dimerization may be a unique regulatory mechanism for lipid chaperones. Structural dynamics and binding of Caenorhabditis elegans lifespan-extending lipid binding protein-3 to polyunsaturated fatty acids.,Cuevas AR, Tillman MC, Wang MC, Ortlund EA Protein Sci. 2025 Jan;34(1):e5249. doi: 10.1002/pro.5249. PMID:39660930[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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