Synaptobrevin transmembrane domain determines the structure and dynamics of the SNARE motif and the linker region.
Biochim Biophys Acta
; 1858(4): 855-65, 2016 Apr.
Article
em En
| MEDLINE
| ID: mdl-26851777
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.
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Base de dados:
MEDLINE
Assunto principal:
Membrana Celular
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Proteínas SNARE
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Proteína 2 Associada à Membrana da Vesícula
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Bicamadas Lipídicas
Limite:
Animals
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article