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Hairpin protein partitioning from the ER to lipid droplets involves major structural rearrangements.
Dhiman, Ravi; Perera, Rehani S; Poojari, Chetan S; Wiedemann, Haakon T A; Kappl, Reinhard; Kay, Christopher W M; Hub, Jochen S; Schrul, Bianca.
Afiliación
  • Dhiman R; Medical Biochemistry and Molecular Biology, Center for Molecular Signaling (PZMS), Faculty of Medicine, Saarland University, 66421, Homburg/Saar, Germany.
  • Perera RS; Medical Biochemistry and Molecular Biology, Center for Molecular Signaling (PZMS), Faculty of Medicine, Saarland University, 66421, Homburg/Saar, Germany.
  • Poojari CS; Theoretical Physics and Center for Biophysics, Saarland University, 66123, Saarbrücken, Germany.
  • Wiedemann HTA; Physical Chemistry and Chemistry Education, Saarland University, 66123, Saarbrücken, Germany.
  • Kappl R; Department of Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), Faculty of Medicine, Saarland University, 66421, Homburg/Saar, Germany.
  • Kay CWM; Physical Chemistry and Chemistry Education, Saarland University, 66123, Saarbrücken, Germany.
  • Hub JS; London Centre for Nanotechnology, University College London, WC1H 0AH, London, UK.
  • Schrul B; Theoretical Physics and Center for Biophysics, Saarland University, 66123, Saarbrücken, Germany.
Nat Commun ; 15(1): 4504, 2024 May 27.
Article en En | MEDLINE | ID: mdl-38802378
ABSTRACT
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Retículo Endoplásmico / Simulación de Dinámica Molecular / Gotas Lipídicas Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Retículo Endoplásmico / Simulación de Dinámica Molecular / Gotas Lipídicas Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido