Exceptional stability of a perilipin on lipid droplets depends on its polar residues, suggesting multimeric assembly
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.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 1 to 8.
Article and author information
Author details
Funding
CNRS (CNRS-PICS No 214454)
- Alenka Čopič
Slovenian Research Agency (No. P1-0055)
- Jure Derganc
Ministere de l'Education National, de l'Enseignement Superieur de la Recherche
- Manuel Giménez-Andrés
Fondation ARC pour la Recherche sur le Cancer (DOC20190509052)
- Manuel Giménez-Andrés
European Research Council (Synergy #856404)
- Bruno Antonny
- Alenka Čopič
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2021, Giménez-Andrés et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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