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Structural insights into perilipin 3 membrane association in response to diacylglycerol accumulation

Author

Listed:
  • Yong Mi Choi

    (Stony Brook University)

  • Dalila Ajjaji

    (ENS, Université PSL, CNRS, Sorbonne Université, Université Paris Cité)

  • Kaelin D. Fleming

    (University of Victoria)

  • Peter P. Borbat

    (Cornell University
    Cornell University)

  • Meredith L. Jenkins

    (University of Victoria)

  • Brandon E. Moeller

    (University of Victoria)

  • Shaveen Fernando

    (Stony Brook University)

  • Surita R. Bhatia

    (Stony Brook University)

  • Jack H. Freed

    (Cornell University
    Cornell University)

  • John E. Burke

    (University of Victoria
    The University of British Columbia)

  • Abdou Rachid Thiam

    (ENS, Université PSL, CNRS, Sorbonne Université, Université Paris Cité)

  • Michael V. Airola

    (Stony Brook University)

Abstract

Lipid droplets (LDs) are dynamic organelles that contain an oil core mainly composed of triglycerides (TAG) that is surrounded by a phospholipid monolayer and LD-associated proteins called perilipins (PLINs). During LD biogenesis, perilipin 3 (PLIN3) is recruited to nascent LDs as they emerge from the endoplasmic reticulum. Here, we analyze how lipid composition affects PLIN3 recruitment to membrane bilayers and LDs, and the structural changes that occur upon membrane binding. We find that the TAG precursors phosphatidic acid and diacylglycerol (DAG) recruit PLIN3 to membrane bilayers and define an expanded Perilipin-ADRP-Tip47 (PAT) domain that preferentially binds DAG-enriched membranes. Membrane binding induces a disorder to order transition of alpha helices within the PAT domain and 11-mer repeats, with intramolecular distance measurements consistent with the expanded PAT domain adopting a folded but dynamic structure upon membrane binding. In cells, PLIN3 is recruited to DAG-enriched ER membranes, and this requires both the PAT domain and 11-mer repeats. This provides molecular details of PLIN3 recruitment to nascent LDs and identifies a function of the PAT domain of PLIN3 in DAG binding.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38725-w
    DOI: 10.1038/s41467-023-38725-w
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    References listed on IDEAS

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