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PreprintCited by 57Lipid metabolism and biosynthesisLipid Membrane Structure and BehaviorProtein Structure and Dynamics

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

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Choi, Yong Mi, Ajjaji, Dalila, Fleming, Kaelin D., Borbat, Peter P., Jenkins, Meredith L., Moeller, Brandon E., Fernando, Shaveen, Bhatia, Surita R., Freed, Jack H., Burke, John E., Thiam, Abdou Rachid, Airola, Michael V.·2022·Nature Communications
DOI 10.1101/2022.11.17.516819PMC PMC10238389

Preprint — published as 10.1038/s41467-023-38725-w · Paper page

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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 analyzed how lipid composition affects PLIN3 recruitment to membrane bilayers and LDs, and the structural changes that occur upon membrane binding. We found 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/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.

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Metadata

Authors
Choi, Y. M., Ajjaji, D., Fleming, K. D., Borbat, P. P., Jenkins, M. L., Moeller, B. E., Fernando, S., Bhatia, S. R., Freed, J. H., Burke, J. E., Thiam, A. R., & Airola, M. V.
Affiliations
  • Stony Brook University (US)
  • Centre National de la Recherche Scientifique (FR)
  • University of Victoria (CA)
  • Cornell University (US)
  • University of British Columbia (CA)
Corresponding author
  • Burke, John E.
  • Thiam, Abdou Rachid
  • Airola, Michael V.
ORCID
Venue
Nature Communications
Publisher
openRxiv
Published
2022-11-17
Volume
14
Issue
1
Pages
3204-3204
ISSN
2041-1723 (ISSN-L)
DOI
10.1101/2022.11.17.516819
PMC
PMC10238389
OpenAlex
W4379184846
Cited by
57
References
1
Citations by year
2026: 19 · 2025: 16 · 2024: 16 · 2023: 6
FWCI
5.74
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Science Foundation (1903189, 1922639)
  • U.S. Department of Health and Human Services (1R24GM146107, R35128666, P41GM103521)
  • Alfred P. Sloan Foundation
  • Government of Canada (Discovery Grant 2020-04241)
  • Michael Smith Health Research BC (2020-04241, 17868)
  • Agence Nationale de la Recherche (ANR-18-CE11-0012, CE11-0032-02-LIPRODYN, 0012-01, ANR-21-CE13-0014, ANR-21-CE11-0032)
  • National Institutes of Health
  • Natural Sciences and Engineering Research Council of Canada (rgpin-2020-04241)
  • National Institute of General Medical Sciences (R35128666, P41GM103521, R35GM128666, R24GM146107)
  • Division of Chemical, Bioengineering, Environmental, and Transport Systems (1903189)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
Keywords
PLIN3, lipid droplets, diacylglycerol, membrane binding, lipid droplet formation, endoplasmic reticulum, phosphatidic acid, protein-lipid interactions
MeSH terms
Perilipin-1, Perilipin-3, Diglycerides, Endoplasmic Reticulum, Triglycerides, Lipid Metabolism, Lipid Droplets

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