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A giant amphipathic helix from a perilipin that is adapted for coating lipid droplets

Author

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  • Alenka Čopič

    (Université Paris Diderot, Sorbonne Paris Cité)

  • Sandra Antoine-Bally

    (Université Paris Diderot, Sorbonne Paris Cité)

  • Manuel Giménez-Andrés

    (Université Paris Diderot, Sorbonne Paris Cité
    Université Paris-Sud, Université Paris-Saclay)

  • César Torre Garay

    (Université Paris Diderot, Sorbonne Paris Cité)

  • Bruno Antonny

    (Université Côte d’Azur, CNRS, IPMC)

  • Marco M. Manni

    (Université Côte d’Azur, CNRS, IPMC)

  • Sophie Pagnotta

    (Université Côte d’Azur, CNRS, IPMC)

  • Jeanne Guihot

    (Université Paris Diderot, Sorbonne Paris Cité)

  • Catherine L. Jackson

    (Université Paris Diderot, Sorbonne Paris Cité)

Abstract

How proteins are targeted to lipid droplets (LDs) and distinguish the LD surface from the surfaces of other organelles is poorly understood, but many contain predicted amphipathic helices (AHs) that are involved in targeting. We have focused on human perilipin 4 (Plin4), which contains an AH that is exceptional in terms of length and repetitiveness. Using model cellular systems, we show that AH length, hydrophobicity, and charge are important for AH targeting to LDs and that these properties can compensate for one another, albeit at a loss of targeting specificity. Using synthetic lipids, we show that purified Plin4 AH binds poorly to lipid bilayers but strongly interacts with pure triglycerides, acting as a coat and forming small oil droplets. Because Plin4 overexpression alleviates LD instability under conditions where their coverage by phospholipids is limiting, we propose that the Plin4 AH replaces the LD lipid monolayer, for example during LD growth.

Suggested Citation

  • Alenka Čopič & Sandra Antoine-Bally & Manuel Giménez-Andrés & César Torre Garay & Bruno Antonny & Marco M. Manni & Sophie Pagnotta & Jeanne Guihot & Catherine L. Jackson, 2018. "A giant amphipathic helix from a perilipin that is adapted for coating lipid droplets," Nature Communications, Nature, vol. 9(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03717-8
    DOI: 10.1038/s41467-018-03717-8
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    Cited by:

    1. Yong Mi Choi & Dalila Ajjaji & Kaelin D. Fleming & Peter P. Borbat & Meredith L. Jenkins & Brandon E. Moeller & Shaveen Fernando & Surita R. Bhatia & Jack H. Freed & John E. Burke & Abdou Rachid Thiam, 2023. "Structural insights into perilipin 3 membrane association in response to diacylglycerol accumulation," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Youping Lin & Haixu Chen & Lei Wang & Jiaojiao Su & Junbo Li & Xin Huang, 2024. "Lipase activated endocytosis-like behavior of oil-in-water emulsion," Nature Communications, Nature, vol. 15(1), pages 1-12, December.

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