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

Abstract

How proteins are targeted to lipid droplets (LDs) and distinguish the LD surface from the surfaces of other organelles is poorly understood, but many contain predicted amphipathic helices (AHs) that are involved in targeting. We have focused on human perilipin 4 (Plin4), which contains an AH that is exceptional in terms of length and repetitiveness. Using model cellular systems, we show that AH length, hydrophobicity, and charge are important for AH targeting to LDs and that these properties can compensate for one another, albeit at a loss of targeting specificity.Using synthetic lipids, we show that purified Plin4 AH binds poorly to lipid bilayers but strongly interacts with pure triglycerides, acting as a coat and forming small oil droplets. Because Plin4 overexpression alleviates LD instability under conditions where their coverage by phospholipids is limiting, we propose that the Plin4 AH replaces the LD lipid monolayer, for example during LD growth.

Proteomic analysis reveals rotator cuff injury caused by oxidative stress

“…The decrease in PLIN4 mRNA in skeletal muscle is related to the decrease in the number and volume of LDs in the SS region, and it is positively related to the genes involved in the de novo synthesis of phospholipids and the concentrations of phospholipids PE and PC. 32 , 44 In proteomics studies, PLIN4 expression was also up-regulated in the subacromion synovium of patients with rotator cuff injury, which further verified the existence of oxidative stress. At the same time, studies have also pointed out that fat infiltration is closely related to muscle atrophy and loss of contractility.…”

Triacylglycerols sequester monotopic membrane proteins to lipid droplets

“…The binding of AHs to LDs is more documented both in vitro and in vivo 9,16,19,[22][23][24] : AHs act as surfactants, favorably adsorbed to the oil/water interface of LDs to decrease the interfacial energy. AHs recognizes a variety of membrane features, such as surface charges, curvature, phospholipid packing defects, and neutral lipids 9,16,19,22,23 . In contrast, much less is known about HDs which target to LDs mostly from the ER membrane through ER-LD connecting bridges [25][26][27] .…”

The Troyer syndrome protein spartin mediates selective autophagy of lipid droplets

“…AHs are often found in cytosolic proteins that interact with the LD surface, where they integrate into the phospholipid monolayer of LDs (23)(24)(25). Spartin contains up to 12 sequence stretches with predicted propensity to form 3-11 AHs (11 amino acids per three turns) (Figure 1, E and G), similar to those found in other LD-binding proteins, such as perilipins and -synuclein (23,26,27). Particularly, the Phyre2 structure prediction revealed that spartin sequences of aa 427-517 shows high sequence and structural similarities to LD targeting AH repeats in α-synuclein (aa 4-93) (26,28).…”