Biophysical Society Thematic Meeting | Ascona, Switzerland

Liposomes, Exosomes, and Virosomes: From Modeling Complex Membrane Processes to Medical Diagnostics and Drug Delivery

Monday Speaker Abstracts

Molecular Steps in SNARE-mediated Membrane Fusion Reinhard Jahn . Max Planck Institute for Biophysical Chemistry, Goettingen, Germany.

Eukaryotic cells are compartmentalized into membrane-enclosed organelles. Most of them are connected with each other by the regulated exchange of transport vesicles that bud from the precursor membrane and are transported to their destination membrane where they dock and fuse. In most (but not all) cases, fusion is carried out by SNAREs that represent an evolutionarily conserved superfamily of small and mostly membrane-anchored proteins. SNAREs are distinguished by a conserved stretch of 60-70 amino acids, termed SNARE-motifs, that are located adjacent to the membrane anchor domain. During fusion, four of such SNARE motifs, each belonging to a different subfamily, align with each other to form a highly stable coiled-coil of α-helices. Complex formation proceeds from the N-terminal end towards the C-terminal membrane anchors, thus pulling the membranes together and initiating fusion (“zipper” hypothesis of SNARE function). The steps of SNARE assembly are controlled by members of conserved protein families such as the SM- and CATCHR-proteins, with additional proteins being involved in regulated exocytosis. In our own work, we have focused on understanding the mechanisms of SNARE assembly and SNARE-induced fusion using structural and biochemical approaches and in-vitro fusion reactions with native and artificial membranes. Furthermore, we have recently extended our work towards SNARE-“mimetics”, including SNARE-like synthetic molecules with artificially designed adhesion domains as well as membrane proteins of bacterial pathogens that are capable of substituting for endogenous SNAREs. We hope to achieve a better understanding of the energy landscape of the fusion pathway, thus shedding more light on a reaction fundamental to all eukaryotic cells.

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