v-SNARE transmembrane domains function as catalysts for vesicle fusion.

Dhara M, Yarzagaray A, Makke M, Schindeldecker B, Schwarz Y, Shaaban A, Sharma S, Böckmann R, Lindau M, Mohrmann R, Bruns D (2016)

Publication Language: English

Publication Status: Published

Publication Type: Journal article, Original article

Publication year: 2016

Journal

eLife eLife Sciences Publications

Book Volume: 5

DOI: 10.7554/eLife.17571

Open Access Link: https://elifesciences.org/content/5/e17571

Abstract

Vesicle fusion is mediated by assembly of SNARE proteins between opposing membranes, but it is unknown whether transmembrane domains (TMDs) of SNARE proteins serve mechanistic functions that go beyond passive anchoring of the force-generating SNAREpin to the fusing membranes. Here, we show that conformational flexibility of synaptobrevin-2 TMD is essential for efficient Ca2(+)-triggered exocytosis and actively promotes membrane fusion as well as fusion pore expansion. Specifically, introduction of helix-stabilizing leucine residues within the TMD region spanning the vesicle's outer leaflet strongly impairs exocytosis and decelerates fusion pore dilation. In contrast, increasing the number of helix-destabilizing, ß-branched valine or isoleucine residues within the TMD restores normal secretion but accelerates fusion pore expansion beyond the rate found for the wildtype protein. These observations provide evidence that the synaptobrevin-2 TMD catalyzes the fusion process by its structural flexibility, actively setting the pace of fusion pore expansion.

Authors with CRIS profile

Rainer Böckmann Professur für Computational Biology

Involved external institutions

Universitätsklinikum des Saarlandes (UKS) DE Germany (DE) Universität des Saarlandes (UdS) DE Germany (DE) Max-Planck-Institut für biophysikalische Chemie (Karl-Friedrich-Bonhoeffer-Institut) / Max Planck Institute for Biophysical Chemistry DE Germany (DE)

How to cite

APA:

Dhara, M., Yarzagaray, A., Makke, M., Schindeldecker, B., Schwarz, Y., Shaaban, A.,... Bruns, D. (2016). v-SNARE transmembrane domains function as catalysts for vesicle fusion. eLife, 5. https://dx.doi.org/10.7554/eLife.17571

MLA:

Dhara, Madhurima, et al. "v-SNARE transmembrane domains function as catalysts for vesicle fusion." eLife 5 (2016).

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