TY - JOUR
T1 - Double-Transmembrane Domain of SNAREs Decelerates the Fusion by Increasing the Protein-Lipid Mismatch
AU - Bu, Bing
AU - Tian, Zhiqi
AU - Li, Dechang
AU - Zhang, Kai
AU - Chen, Wei
AU - Ji, Baohua
AU - Diao, Jiajie
N1 - Publisher Copyright:
© 2023 Elsevier Ltd
PY - 2023/7/1
Y1 - 2023/7/1
N2 - 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.
AB - 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.
KW - membrane fusion
KW - protein-lipid mismatch
KW - transmembrane domain
UR - http://www.scopus.com/inward/record.url?scp=85153088809&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85153088809&partnerID=8YFLogxK
U2 - 10.1016/j.jmb.2023.168089
DO - 10.1016/j.jmb.2023.168089
M3 - Article
C2 - 37030649
AN - SCOPUS:85153088809
SN - 0022-2836
VL - 435
JO - Journal of Molecular Biology
JF - Journal of Molecular Biology
IS - 13
M1 - 168089
ER -