Repository logo

Conserved Amphipathic Helices Mediate Lipid Droplet Targeting of Perilipins 1-3.

Change log


Rowe, Emily R 
Mimmack, Michael L 
Barbosa, Antonio D 
Haider, Afreen 
Isaac, Iona 


Perilipins (PLINs) play a key role in energy storage by orchestrating the activity of lipases on the surface of lipid droplets. Failure of this activity results in severe metabolic disease in humans. Unlike all other lipid droplet-associated proteins, PLINs localize almost exclusively to the phospholipid monolayer surrounding the droplet. To understand how they sense and associate with the unique topology of the droplet surface, we studied the localization of human PLINs inSaccharomyces cerevisiae,demonstrating that the targeting mechanism is highly conserved and that 11-mer repeat regions are sufficient for droplet targeting. Mutations designed to disrupt folding of this region into amphipathic helices (AHs) significantly decreased lipid droplet targetingin vivoandin vitro Finally, we demonstrated a substantial increase in the helicity of this region in the presence of detergent micelles, which was prevented by an AH-disrupting missense mutation. We conclude that highly conserved 11-mer repeat regions of PLINs target lipid droplets by folding into AHs on the droplet surface, thus enabling PLINs to regulate the interface between the hydrophobic lipid core and its surrounding hydrophilic environment.



11-mer repeat, amphipathic helix, lipid droplet, lipodystrophy, lipolysis, membrane, membrane targeting, monolayer, perilipin, phospholipid, Amino Acid Sequence, Animals, Binding Sites, Biological Transport, COS Cells, Carrier Proteins, Chlorocebus aethiops, Gene Expression, Humans, Hydrophobic and Hydrophilic Interactions, Lipid Droplets, Membrane Proteins, Micelles, Models, Molecular, Molecular Sequence Data, Mutation, Perilipin-1, Perilipin-2, Perilipin-3, Phosphoproteins, Protein Binding, Protein Interaction Domains and Motifs, Protein Structure, Secondary, Protein Transport, Recombinant Proteins, Saccharomyces cerevisiae, Sequence Alignment, Transgenes, Vesicular Transport Proteins

Journal Title

J Biol Chem

Conference Name

Journal ISSN


Volume Title



Elsevier BV
Medical Research Council (G0701446)
Medical Research Council (MC_UU_12012/5)
Wellcome Trust (107064/Z/15/Z)
Wellcome Trust (091551/Z/10/A)
Medical Research Council (MC_PC_12012)
This work was supported by grants from The Wellcome Trust (091551 and 107064 to DBS), the U.K. NIHR Cambridge Biomedical Research Centre, the Medical Research Council (G0701446 to SS and a Doctoral training grant awarded to the University of Cambridge for ERR), core facilities at the MRC Metabolic Diseases Unit (MC_UU_12012/5) and by the Innovative Medicines Initiative Joint Undertaking, EMIF-Metabolism award.