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

  1. Manuel Giménez-Andrés
  2. Tadej Emeršič
  3. Sandra Antoine-Bally
  4. Juan Martin D'Ambrosio
  5. Bruno Antonny
  6. Jure Derganc
  7. Alenka Čopič  Is a corresponding author
  1. CNRS, Universite de Paris, Universite Paris Saclay, France
  2. University of Ljubljana, Slovenia
  3. CNRS, Universite de Paris, France
  4. CNRS, University of Montpellier, France
  5. Université Côte d'Azur, France

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

  1. Manuel Giménez-Andrés

    Institut Jacques Monod, CNRS, Universite de Paris, Universite Paris Saclay, Paris CEDEX13, France
    Competing interests
    The authors declare that no competing interests exist.
  2. Tadej Emeršič

    Institute of Biophysics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
    Competing interests
    The authors declare that no competing interests exist.
  3. Sandra Antoine-Bally

    Institut Jacques Monod, CNRS, Universite de Paris, Paris CEDEX13, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Juan Martin D'Ambrosio

    CRBM, CNRS, University of Montpellier, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
  5. Bruno Antonny

    CNRS, Institut de Pharmacologie Moléculaire et Cellulaire, Université Côte d'Azur, Valbonne, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9166-8668
  6. Jure Derganc

    Institute of Biophysics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
    Competing interests
    The authors declare that no competing interests exist.
  7. Alenka Čopič

    Institut Jacques Monod, CNRS, Universite de Paris, Paris CEDEX13, France
    For correspondence
    alenka.copic@crbm.cnrs.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0166-7731

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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  1. Manuel Giménez-Andrés
  2. Tadej Emeršič
  3. Sandra Antoine-Bally
  4. Juan Martin D'Ambrosio
  5. Bruno Antonny
  6. Jure Derganc
  7. Alenka Čopič
(2021)
Exceptional stability of a perilipin on lipid droplets depends on its polar residues, suggesting multimeric assembly
eLife 10:e61401.
https://doi.org/10.7554/eLife.61401

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https://doi.org/10.7554/eLife.61401