Hairpin protein partitioning from the ER to lipid droplets involves major structural rearrangements.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
27 May 2024
27 May 2024
Historique:
received:
28
01
2024
accepted:
15
05
2024
medline:
28
5
2024
pubmed:
28
5
2024
entrez:
27
5
2024
Statut:
epublish
Résumé
Lipid droplet (LD) function relies on proteins partitioning between the endoplasmic reticulum (ER) phospholipid bilayer and the LD monolayer membrane to control cellular adaptation to metabolic changes. It has been proposed that these hairpin proteins integrate into both membranes in a similar monotopic topology, enabling their passive lateral diffusion during LD emergence at the ER. Here, we combine biochemical solvent-accessibility assays, electron paramagnetic resonance spectroscopy and intra-molecular crosslinking experiments with molecular dynamics simulations, and determine distinct intramembrane positionings of the ER/LD protein UBXD8 in ER bilayer and LD monolayer membranes. UBXD8 is deeply inserted into the ER bilayer with a V-shaped topology and adopts an open-shallow conformation in the LD monolayer. Major structural rearrangements are required to enable ER-to-LD partitioning. Free energy calculations suggest that such structural transition is unlikely spontaneous, indicating that ER-to-LD protein partitioning relies on more complex mechanisms than anticipated and providing regulatory means for this trans-organelle protein trafficking.
Identifiants
pubmed: 38802378
doi: 10.1038/s41467-024-48843-8
pii: 10.1038/s41467-024-48843-8
doi:
Substances chimiques
Lipid Bilayers
0
Lipid Droplet Associated Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4504Subventions
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : CRC1027 project C9
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : INST 256/535-1
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : CRC 1027 project B7
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : INST 256/539-1
Informations de copyright
© 2024. The Author(s).
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