Structural dynamics of the intrinsically disordered SNARE proteins at the membrane interface: Recent insights by a combined solution and solid-state NMR approach
Tobias Stief1, Mirko Kraus2, Reinhard Jahn3, Angel Perez-Lara4, Nils-Alexander Lakomek2
1Forschungszentrum Jülich, IBI-7: Strukturbiochemie, Jülich, Germany,
2Heinrich Heine University Düsseldorf, Physikalische Biologie, Düsseldorf, Germany,
3Max Planck Institute for Multidisciplinary Sciences (Faßberg-Campus), Neurobiologie, Göttingen, Germany,
4University of Granada, Physical Chemistry, Granada, Spain
Neurotransmitter release at the neuronal synapse is a fundamental process for signal transduction between neurons. The SNARE proteins play a crucial role here by eliciting the fusion of the synaptic vesicle membrane with the presynaptic plasma membrane. A fusion pore will open, and the neurotransmitters are released into the synaptic cleft. In their pre-fusion state, the SNARE proteins are intrinsically disordered. They do not exhibit a well-defined structure and show high internal flexibility. The SNARE proteins are membrane-anchored. However, the mode of interaction between the SNARE proteins and the lipid membrane is not well understood. Here NMR spectroscopy can provide novel structural and dynamic insights at an atomic resolution, as NMR is favorably suited for studying highly dynamic systems, such as intrinsically disordered proteins. We use the SNARE proteins as a model system for developing novel NMR methods to characterize the inner and conformational dynamics of intrinsically disordered proteins that interact with lipid membranes or a membrane-anchored. We address a large range of timescales, from pico- to milliseconds. We employ both solution NMR and proton- detected solid-state NMR methods at very fast MAS (magic angle spinning) frequencies. The aim is to better describe the conformational space of intrinsically disordered proteins at the lipid membrane interface. At the conference, we will present recent (unpublished) insights into the structural dynamics of the SNARE proteins synaptobrevin-2 and SNAP25 at the lipid membrane interface.