Developmental Cell
Volume 44, Issue 1, 8 January 2018, Pages 73-86.e4
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Article
Mechanism and Determinants of Amphipathic Helix-Containing Protein Targeting to Lipid Droplets

https://doi.org/10.1016/j.devcel.2017.12.011Get rights and content
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Highlights

  • Lipid droplet surfaces are characterized by phospholipid packing defects

  • Packing defects recruit amphipathic helices to the lipid droplet surface

  • Large, hydrophobic residues of amphipathic helices initially bind packing defects

  • In isolation, many amphipathic helices accumulate on lipid droplets

Summary

Cytosolic lipid droplets (LDs) are the main storage organelles for metabolic energy in most cells. They are unusual organelles that are bounded by a phospholipid monolayer and specific surface proteins, including key enzymes of lipid and energy metabolism. Proteins targeting LDs from the cytoplasm often contain amphipathic helices, but how they bind to LDs is not well understood. Combining computer simulations with experimental studies in vitro and in cells, we uncover a general mechanism for targeting of cytosolic proteins to LDs: large hydrophobic residues of amphipathic helices detect and bind to large, persistent membrane packing defects that are unique to the LD surface. Surprisingly, amphipathic helices with large hydrophobic residues from many different proteins are capable of binding to LDs. This suggests that LD protein composition is additionally determined by mechanisms that selectively prevent proteins from binding LDs, such as macromolecular crowding at the LD surface.

Keywords

lipid droplets
amphipathic helices
protein targeting
phospholipid bilayers
phospholipid monolayers
phospholipid packing defects
all-atom molecular dynamics simulations
cell biology
reconstitution assay

Cited by (0)

6

Present address: Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA

7

Present address: Pharmaceutical Product Development, Inc., Middleton, WI 53562, USA

8

These authors contributed equally

9

Senior authors

10

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