SNARE zippering requires activation by SNARE-like peptides in Sec1/Munc18 proteins

作者：Yu, Haijia; Shen, Chong; Liu, Yinghui; Menasche, Bridget L.; Ouyang, Yan; Stowell, Michael H. B.^*; Shen, Jingshi^*

来源：Proceedings of the National Academy of Sciences, 2018, 115(36): E8421-E8429.

DOI：10.1073/pnas.1802645115

• SNARE
• membrane fusion
• vesicle fusion
• exocytosis
• SM protein

Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) catalyze membrane fusion by forming coiled-coil bundles between membrane bilayers. The SNARE bundle zippers progressively toward the membranes, pulling the lipid bilayers into close proximity to fuse. In this work, we found that the +1 and +2 layers in the C-terminal domains (CTDs) of SNAREs are dispensable for reconstituted SNARE-mediated fusion reactions. By contrast, all CTD layers are required for fusion reactions activated by the cognate Sec1/Munc18 (SM) protein or a synthetic Vc peptide derived from the vesicular (v-) SNARE, correlating with strong acceleration of fusion kinetics. These results suggest a similar mechanism underlying the stimulatory functions of SM proteins and Vc peptide in SNARE-dependent membrane fusion. Unexpectedly, we identified a conserved SNARE-like peptide (SLP) in SM proteins that structurally and functionally resembles Vc peptide. Like Vc peptide, SLP binds and activates target (t-) SNAREs, accelerating the fusion reaction. Disruption of the t-SNARE-SLP interaction inhibits exocytosis in vivo. Our findings demonstrated that a t-SNARE-SLP intermediate must form before SNAREs can drive efficient vesicle fusion.

• 出版日期2018-9-4
• 单位南京师范大学