Double-Transmembrane Domain of SNAREs Decelerates the Fusion by Increasing the Protein-Lipid Mismatch

Bing Bu, Zhiqi Tian, Dechang Li, Kai Zhang, Wei Chen, Baohua Ji, Jiajie Diao

Research output: Contribution to journalArticlepeer-review

Abstract

SNARE is the essential mediator of membrane fusion that highly relies on the molecular structure of SNAREs. For instance, the protein syntaxin-1 involved in neuronal SNAREs, has a single transmembrane domain (sTMD) leading to fast fusion, while the syntaxin 17 has a V-shape double TMDs (dTMDs), taking part in the autophagosome maturation. However, it is not clear how the TMD structure influences the fusion process. Here, we demonstrate that the dTMDs significantly reduce fusion rate compared with the sTMD by using an in vitro reconstitution system. Through theoretical analysis, we reveal that the V-shape dTMDs can significantly increase protein-lipid mismatch, thereby raising the energy barrier of the fusion, and that increasing the number of SNAREs can reduce the energy barrier or protein-lipid mismatch. This study provides a physicochemical mechanistic understanding of SNARE-regulated membrane fusion.

Original languageEnglish (US)
Article number168089
JournalJournal of Molecular Biology
Volume435
Issue number13
DOIs
StatePublished - Jul 1 2023

Keywords

  • membrane fusion
  • protein-lipid mismatch
  • transmembrane domain

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Molecular Biology

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