Insertion of perilipin 3 into a glycero(phospho)lipid monolayer depends on lipid headgroup and acyl chain species

Abstract

function of LDs. While much work has focused on peripheral and integral membrane proteins, the mechanism by which LD binding proteins recognize and target to LDs is still poorly understood (1). This is especially true for dedicated LD binding proteins of the perilipin family, i.e., perilipin 1 through 5, that function in the biogenesis and metabolism (lipolysis) of LDs. No work has directly investigated the interaction of a perilipin family member with a phospholipid monolayer interface. In order to address how this family of proteins interacts with lipid interfaces, we investigated the interaction of perilipin 3 with phospholipid monolayers at the air-buffer interface. We chose perilipin 3 because it is found in the cytosol as well as on the LD surface, and because previous work has characterized the structure and LD association of the protein (1-3).In addition to providing cellular energy, LDs take part in many other cellular functions, including signal transduction, formation of new cellular membranes, hormone synthesis, and lipid trafficking (4-8). Under certain physiological conditions, LDs have been found to act as storehouses for several different types of enzymes and proteins, including histones (9, 10), and they also facilitate virus replication (11-13). An understanding of how proteins Lipid droplets (LDs) are dynamic cell organelles that carry out a multitude of cellular functions vital for life, and protein-lipid interactions are crucial to the structure and

Visualization of lipid directed dynamics of perilipin 1 in human primary adipocytes

“…It is also interesting that a strong protein-lipid interaction is observed with the ordered (gel phase) DPPC, whereas the protein has very limited binding affinity with the liquid disordered (fluid phase) DOPC phospholipid. While structural data on PLIN1 is still lacking, functional studies suggest that both PLIN2 and PLIN3 contain independent, non-overlapping, lipid-binding sites involving the 11-mer amphipathic helical motif that is common to all perilipins, including PLIN1 32 , 33 . PLIN1 additionally has a hydrophobic motif that mediate lipid droplet targeting independently 34 .…”

The perilipin family of lipid droplet proteins: Gatekeepers of intracellular lipolysis

“…How the perilipin family members recognize and target to lipid droplets with specific lipid content and whether interactions with the surface phospholipid monolayer direct perilipin targeting remain largely unanswered questions, although a recent study has revealed that the acyl chain saturation of phospholipids affects the interaction of recombinant truncated forms of perilipin 3 with phospholipid monolayers of varying composition in vitro (6). To date, few studies have addressed the biophysics of the phospholipid and protein surface properties of lipid droplets.…”

A giant amphipathic helix from a perilipin that is adapted for coating lipid droplets

“…Lipid packing and membrane curvature promote AH recruitment through creation of lipid packing defects, which have been analyzed extensively in bilayer membranes 18 – 20 . It is not clear which parameters are important for AH binding to the LD surface 21 . A recent in silico analysis suggests that whereas an LD phospholipid monolayer at zero surface tension does not behave very differently from a bilayer, lipid packing defects increase non-linearly with increasing surface tension of the monolayer 22 .…”