Synaptobrevin transmembrane domain determines the structure and dynamics of the SNARE motif and the linker region.
Han J, Pluhackova K, Bruns D, Böckmann R (2016)
Publication Language: English
Publication Status: Published
Publication Type: Journal article
Publication year: 2016
Journal
Publisher: Elsevier
Book Volume: 1858
Pages Range: 855-65
Journal Issue: 4
DOI: 10.1016/j.bbamem.2016.01.030
Abstract
The vesicular protein synaptobrevin II (sybII) constitutes a central component of the SNARE complex, which mediates vesicle fusion in neuronal exocytosis. Previous studies revealed that the transmembrane domain (TMD) of sybII is playing a critical role in the fusion process and is involved in all distinct fusion stages from priming to fusion pore opening. Here, we analyzed sequence-dependent effects of sybII and of mutants of sybII on both structure and flexibility of the protein and the interactions with a phospholipid bilayer by means of microsecond atomistic simulations. The sybII TMD was found to direct the folding of both the juxtamembrane helix and of the connecting linker and thus to influence both the intrinsic helicity and flexibility. Fusion active peptides revealed two helical segments, one for the juxtamembrane region and one for the TMD, connected by a flexible linker. In contrast, a fusion-inactive poly-leucine TMD mutant assumes a structure with a comparably rigid linker that is suggested to hinder the formation of the trans-SNARE complex during fusion. Kinking of the TMD at the central glycine together with anchoring of the TMD via conserved tryptophans and a lysine in position 94 likely yields an enhanced flexibility of sybII for different membrane thickness. All studied peptides were found to deform the outer membrane layer by altering the lipid head group orientation, causing partial membrane dehydration and enhancing lipid protrusions. These effects weaken the integrity of the outer membrane layer and are attributed mainly to the highly charged linker and JM regions of sybII.
Authors with CRIS profile
Jing Han
Professur für Computational Biology
Kristyna Pluhackova
Professur für Computational Biology
Rainer Böckmann
Professur für Computational Biology
Involved external institutions
Germany (DE)How to cite
APA:
Han, J., Pluhackova, K., Bruns, D., & Böckmann, R. (2016). Synaptobrevin transmembrane domain determines the structure and dynamics of the SNARE motif and the linker region. BBA - Biochimica et Biophysica Acta, 1858(4), 855-65. https://doi.org/10.1016/j.bbamem.2016.01.030
MLA:
Han, Jing, et al. "Synaptobrevin transmembrane domain determines the structure and dynamics of the SNARE motif and the linker region." BBA - Biochimica et Biophysica Acta 1858.4 (2016): 855-65.
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