Determinants of Endoplasmic Reticulum-to-Lipid Droplet Protein Targeting.

ABSTRACT: Lipid droplet (LD) formation from the endoplasmic reticulum (ER) is accompanied by the targeting and accumulation of specific hydrophobic, membrane-embedded proteins on LDs. The determinants of this process are unknown. Here, we study the hydrophobic membrane motifs of two Drosophila melanogaster proteins, GPAT4 and ALG14, that utilize this pathway, and we identify crucial sequence features that mediate LD accumulation. Molecular dynamics simulations and studies in cells reveal that LD targeting of these motifs requires deeply inserted tryptophans that have lower free energy in the LD oil phase and positively charged residues near predicted hairpin hinges that become less constrained in the LD environment. Analyzing hydrophobic motifs from similar LD-targeting proteins, it appears that the

SUBMITTER: Olarte MJ 

PROVIDER: S-EPMC7696655 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature