AUTHOR=Hu Yaru , Zhu Le , Ma Cong 

TITLE=Structural Roles for the Juxtamembrane Linker Region and Transmembrane Region of Synaptobrevin 2 in Membrane Fusion

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2020.609708

DOI=10.3389/fcell.2020.609708

ISSN=2296-634X

ABSTRACT=<p>Formation of the <italic>trans</italic>-SNARE complex is believed to generate a force transfer to the membranes to promote membrane fusion, but the underlying mechanism remains elusive. In this study, we show that helix-breaking and/or length-increasing insertions in the juxtamembrane linker region of synaptobrevin-2 exert diverse effects on liposome fusion, in a manner dependent on the insertion position relative to the two conserved tryptophan residues (W<sup>89</sup>/W<sup>90</sup>). Helical extension of synaptobrevin-2 to W<sup>89</sup>/W<sup>90</sup> is a prerequisite for initiating membrane merger. The transmembrane region of synaptobrevin-2 enables proper localization of W<sup>89</sup>/W<sup>90</sup> at the membrane interface to gate force transfer. Besides, our data indicate that the SNARE regulatory components Munc18-1 and Munc13-1 impose liposome fusion strong demand on tight coupling between the SNARE motif and the transmembrane region of synaptobrevin-2.</p>