Dhiman, Ravi;
Perera, Rehani S;
Poojari, Chetan S;
Wiedemann, Haakon TA;
Kappl, Reinhard;
Kay, Christopher WM;
Hub, Jochen S;
(2024)
Hairpin protein partitioning from the ER to lipid droplets involves major structural rearrangements.
Nature Communications
, 15
, Article 4504. 10.1038/s41467-024-48843-8.
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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.
| Type: | Article |
|---|---|
| Title: | Hairpin protein partitioning from the ER to lipid droplets involves major structural rearrangements |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41467-024-48843-8 |
| Publisher version: | https://doi.org/10.1038/s41467-024-48843-8 |
| Language: | English |
| Additional information: | © The Author(s), 2024. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. https://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Biophysical chemistry, Cell biology, Membrane proteins, Molecular conformation, Molecular modelling. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > London Centre for Nanotechnology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10221185 |
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