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Proposing Institution

Biopolymer Chemistry,TU München
Project Manager

Dr. Christina Scharnagl
Maximum von Imhof Forum 4
85354 Freising
Thinking, memory, and motion rely on fast and precise communication between neurons. Release of neurotransmitters - the key to interneuronal communication - is mediated by fusion of synaptic vesicles with the plasma membrane in response to an action potential. A highly specialized engine, the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) complex, plays a key role in vesicle fusion. One significant challenge in current SNARE research is to identify the molecular mechanisms that determine the intrinsic dynamics of their transmembrane domains and to relate them to their apparent role in membrane fusion. Studying natural SNARE transmembrane domains in comparison to hybrids of SNARE transmembrane helices and low-complexity helical model peptides we will investigate the fundamental questions of how peptide/lipid interactions of SNARE proteins perturb bilayer organisation and thus prime membranes for fusion? We will use a serial multi-scale modeling approach, where coarse-grained molecular dynamic runs are used for the rather slow process of lipid bilayer self assembly around the transmembrane helices followed by all-atom simulations in order to study the peptide/lipid interaction and lipid organisation and dynamics in atomistic detail. In sum, we expect to be able to delineate the connections between crucial features of fusion protein transmembrane domains and their ability to change the surrounding membrane in order to understand the mechanism by which membrane fusion is initated.

Impressum, Conny Wendler