The process of peptide-mediated liposomalįusion and lipopeptide structures. Lead to competing peptide interactions, which provides an equilibriumīetween K 3–E 3 coiled-coil formation and Into close proximity, allowing fusion to occur. Of the membrane and initiation of the fusion process, whereas E 3 facilitates coiled-coil formation, bringing the membranes 35, 36 This K 3–membrane interaction leads to destabilization Hydrophobic face that comprises leucine and isoleucine residues butĪlso via the flanking lysine residues in a process known as snorkeling. 35 A key function of K 3 is its interaction with the liposome membrane, primarily via its A recent study hasĪlso proposed an asymmetric role for the peptides in the fusion process,Īs illustrated in Figure Figure1 1. 32 Conversely, the parallel or antiparallel coiled-coil orientation 33 and coiled-coil oligomer state 34 did not influence the rate of fusion. Increasing the length of the peptide (which increases theĬoiled-coil binding strength and peptide–membrane interactions)Īlso has a positive effect on the fusion efficiency. The consequences of the anchor type were previously investigated, 31 and it was shown that only DOPE and cholesterolĪnchors yielded significant fusion, with the latter being the mostĮfficient. Modifications and their resulting influence on fusion efficiency. Is revealed by studying the relationship between rational lipopeptide (DOPE), (L), and this is conjugated to the peptide via a PEG spacer 29, 30 These peptides are held in lipid membranes by a lipid anchor, eitherĬholesterol (C) or 1,2-dioleoyl- sn-glycero-3-phosphoethanol-amine With the lipidated heterodimeric coiled-coil pair E 3 (EIAALEK) 3 and K 3 (KIAALKE) 3 as fusogens. 25− 28 In our laboratory, a model system for membrane fusion has been developed Such systems are primarily based on phospholipid vesiclesįunctionalized with either DNA, 11− 15 peptides, 16− 19 or small molecules 20− 24 that act as recognition motifs, but molecular recognition betweenįunctionalized cyclodextrin vesicles has also been reported. Using the natural proteins 7− 10 and has served as an inspiration for the design of 6 This SNARE fusion system has been studied extensively I.e., lipid mixing or hemifusion and (3) formation of a fusion pore,įacilitating content mixing between the two fused compartments. Of the membrane at the site of contact (2) merging of outer membranes, Process, consists of three more steps: 4, 5 (1) disruption The fusion cascade, initiated by this docking They form a tetrameric coiled-coil, which brings the opposing membranes On opposing membranes, and in the first step of the fusion process, 1− 3 Complementary SNARE protein subunits are located SNARE (soluble N-ethylmaleimide-sensitiveįactor (NSF) attachment protein receptor) proteins are a well conservedĬlass of fusion proteins that are primarily involved in vesicle traffickingĪnd fusion. Interactions and thus mediates fusion more efficiently. Structure a cholesterol anchor appears to enhance K 3–membrane Both the anchor type and spacer length affect the peptide Over time by improving the peptide accessibility for successive fusionĮvents. However, a PEG 12 spacer increases the fusion efficiency K 3 directs the fusion process via peptide–membrane interactions,īut the length of the PEG spacer plays two competing roles: a PEG 4/PEG 8 spacer length is optimal for membrane destabilization The efficacy of thisĮ 3 handle is enhanced by longer spacer lengths. We conclude that negatively charged E 3 acts as a “handle” for positively charged K 3 and facilitates liposome docking, the first stage of theįusion process, through coiled-coil formation. Our resultsĭemonstrate the asymmetric role of the peptides in the fusion processīecause alterations to the PEG spacer length affect E 3 and On peptide secondary structure, their interactions with liposomes,Īnd their ability to mediate fusion were studied using a variety ofĭifferent content mixing experiments and CD spectroscopy. The influence of the PEG spacer length, coupled with the type of lipidĪnchor, on liposome–liposome fusion. Poly(ethylene glycol) (PEG) spacer, and this contribution studies In this system, peptides are conjugated to a lipid anchor via a Lipidated derivatives of a heterodimeric coiled-coil pair dubbed E 3 (EIAALEK) 3 and K 3 (KIAALKE) 3. Have developed a model system for membrane fusion that utilizes
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