Wrapping up the fats-a structure of the lipid droplet biogenesis protein seipin

Abstract

The lipid droplet (LD) biogenesis protein seipin is crucial for formation of normal LDs, but its exact functional role has been enigmatic. In this issue, Sui et al. (2018. J. Cell Biol. https://doi.org/10.1083/jcb.201809067) report the cryo--electron microscopy structure of seipin, which provides novel insights into how seipin might mediate LD formation.

Figure 1.

Hypothetical model of the molecular function of seipin. (A) Seipin oligomers anchored within the phospholipid (PL) bilayer of the ER via their transmembrane domains (dark blue) move within the plane of the membrane and scan its surface from both sides with hydrophobic cytosolic (red) and luminal (not depicted) helices that bind preferentially to lipid packing defects in the PL monolayer of lipid lenses and LDs. (B) Upon encountering a lipid lens, the seipin complex binds to the monolayer surface via its hydrophobic helices (red) and supports growth of the emerging LD by anchoring it to the ER bilayer. The putative LBD (green) may have a role in lipid transfer, signaling, or regulation of PL metabolism.