CUED Publications database

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

Rowe, ER and Mimmack, ML and Barbosa, AD and Haider, A and Isaac, I and Ouberai, MM and Thiam, AR and Patel, S and Saudek, V and Siniossoglou, S and Savage, DB (2016) Conserved Amphipathic Helices Mediate Lipid Droplet Targeting of Perilipins 1-3. J Biol Chem, 291. pp. 6664-6678.

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Abstract

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.

Item Type: Article
Uncontrolled Keywords: 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 Cercopithecus 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
Subjects: UNSPECIFIED
Divisions: Div B > Solid State Electronics and Nanoscale Science
Depositing User: Cron Job
Date Deposited: 17 Jul 2017 18:57
Last Modified: 17 Oct 2017 01:39
DOI: