Mechanism and Determinants of Amphipathic Helix-Containing Protein Targeting to Lipid Droplets

Publication date: 8 January 2018
Source:Developmental Cell, Volume 44, Issue 1
Author(s): Coline Prévost, Morris E. Sharp, Nora Kory, Qingqing Lin, Gregory A. Voth, Robert V. Farese, Tobias C. Walther
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.

Graphical abstract

Teaser

Prévost, Sharp, et al. explore how cytosolic proteins target the surface of lipid droplets (LDs). A distinctive surface structure makes LDs suited to recruiting large hydrophobic amino acid-enriched protein motifs. Rather than specific LD protein-targeting mechanisms, regulation is likely at the level of preventing promiscuous association by non-LD proteins.


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