ABSTRACT
Membrane fusion mediated by Soluble N-ethylmaleimide-sensitive factor activating protein receptor (SNARE) proteins is an important cellular process. For neuronal SNAREs, the single transmembrane domain has been proposed to pass zippering energy to membranes for inducing fast fusion. In contrast, the SNARE protein, syntaxin 17, for membrane fusion involved in autophagosome maturation contains an unusual V-shape double-transmembrane domain that may influence its capability to pass energy. Here, we showed that this double-transmembrane domain significantly reduces fusion with an in vitro reconstitution system. Through theoretic modelling, we found that this V-shape double-transmembrane domain increases lipid-protein mismatch, which reduces the energy transduction for fusion. Moreover, our model also revealed the involvement of 2-3 SNAREs in a general fusion process.
SIGNIFICANT STATEMENT Soluble N-ethylmaleimide-sensitive factor activating protein receptors (SNAREs) serve as the molecular machine to mediate membrane fusion. The zipper formation of core structure extending to membranes by two single transmembrena domains (TMDs) is the main driving force of membrane fusion. The role of TMD in fusion is unclear. By adding an extra TMD, we found that the hydrophobic mismatch effect between the thickness of the membrane and the length of TMDs plays an important role in regulating fusion.