Disorder-to-order transition of synaptobrevin-2 - a key player in neuronal exocytosis, Projekt 1, GRK 2467

Syb is a SNARE protein forming, together with SNAP-25 and syntaxin-1, the SNARE fusion complex during neuronal exocytosis. It contains a small integral membrane helix and a large cytosolic domain. In the fusion complex, this cytosolic domain is part of a helix bundle, however, it is natively disordered in the absence of other SNARE proteins. Previous studies in the presence of lipids revealed helical segments flanked by disordered regions representing functionally important intermediates for SNARE complex formation. As such, N-terminal nascent helical segments are thought to drive membrane fusion by zippering SNARE proteins into the folded complex, whereas internally disordered regions supposedly provide the flexibility required for trans-to-cis conversion of the SNARE complex during membrane merging. Studying the natively disordered states of Syb and the intermediates of SNARE complex formation will provide insights into the functionality of disorder during membrane fusion.