Biophysical Society Thematic Meeting

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.