Exceptional stability of a perilipin on lipid droplets depends on its polar residues, suggesting multimeric assembly

Published on May 7, 2021 Updated on May 7, 2021

Manuel Giménez-Andrés, Tadej Emeršič, Sandra Antoine-Bally, Juan Martin D'Ambrosio, Bruno Antonny, Jure Derganc, Alenka Čopič eLife 2021

Abstract

Numerous proteins target lipid droplets (LDs) through amphipathic helices (AHs). It is generally assumed that AHs insert bulky hydrophobic residues in packing defects at the LD surface. However, this model does not explain the targeting of perilipins, the most abundant and specific amphipathic proteins of LDs, which are weakly hydrophobic. A striking example is Plin4, whose gigantic and repetitive AH lacks bulky hydrophobic residues. Using a range of complementary approaches, we show that Plin4 forms a remarkably immobile and stable protein layer at the surface of cellular or in vitro generated oil droplets, and decreases LD size. Plin4 AH stability on LDs is exquisitely sensitive to the nature and distribution of its polar residues. These results suggest that Plin4 forms stable arrangements of adjacent AHs via polar/electrostatic interactions, reminiscent of the organization of apolipoproteins in lipoprotein particles, thus pointing to a general mechanism of AH stabilization via lateral interactions.

Gimenez-Andres et al. eLife 2021;10:e61401

PMID: 33856341
DOI: 10.7554/eLife.61401