A revisit of the conformational dynamics of SNARE protein rYkt6

Abstract N -ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins are involved in the fusion of vesicles with their target membranes. R-SNARE protein Ykt6 is one of the most conserved SNARE in eukaryotes. The conformational state of Ykt6 is regulated by the lipidations at its C-terminal motif. Previous studies show that the binding of dodecylphosphocholine (DPC) can stabilize a closed conformation of rat Ykt6 ( r Ykt6) and mimic the farnesylated r Ykt6. Despite this model, the detailed conformational dynamics of Ykt6 is still unclear. Here, we combined smFRET and MD simulation to demonstrate that the un-lipidated r Ykt6 adopts five major conformational states. DPC binding shifts the conformational distribution toward the more closed states. At the same time, there remain considerable fractions of open and semi-open conformations in the presence of DPC. These newly revealed dynamic features of r Ykt6 are consistent with its unique functional diversity in neuronal cells.