Universiteit Leiden

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Zipping into Fusion

Promotor: Prof.dr. J.G.E.M. Fraaije, Co-promotor: A. Kros

T. Zheng
17 december 2014
Thesis in Leiden Repository

Fusion of lipid bilayers in cells facilitates the active transport of chemicals. Non-viral membrane fusion is regulated by a cascade of proteins as the process is highly regulated both in space and time. In eukaryotic cells, the so-called SNARE protein complex is at the heart of fusion. However, little is known about the actual mechanism at the molecular level. Inspired by the SNARE protein complex, our group previously developed a model system composed of a pair of lipidated complementary coiled coil peptides enabling targeted liposome-liposome fusion. This model system possesses all the key characteristics of membrane fusion similar to SNARE mediated fusion. The tetrameric coiled-coil of SNAREs is mimicked by a complementary pair of coiled coil forming peptides composed of three heptad repeat units (denoted “coil-E” and “coil-K”). A flexible poly(ethylene glycol) spacer is conjugated to the N-terminus ensuring rotational freedom of the peptides. Lipidation warrants the anchoring of the peptides in the membrane by means of a phospholipid anchor (DOPE), mimicking the transmembrane domain of SNAREs. In order to develop future applications of this model system, the mechanism of membrane fusion needs to be studied in more detail and this has been the goal of this thesis.