Exploring the conformational changes of the Munc18-1/syntaxin 1a complex.

Details

Serval ID
serval:BIB_46EE05B7E159
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Exploring the conformational changes of the Munc18-1/syntaxin 1a complex.
Journal
Protein science
Author(s)
Stefani I., Iwaszkiewicz J., Fasshauer D.
ISSN
1469-896X (Electronic)
ISSN-L
0961-8368
Publication state
In Press
Peer-reviewed
Oui
Language
english
Notes
Publication types: Journal Article
Publication Status: aheadofprint
Abstract
Neurotransmitters are released from synaptic vesicles, the membrane of which fuses with the plasma membrane upon calcium influx. This membrane fusion reaction is driven by the formation of a tight complex comprising the plasma membrane SNARE proteins syntaxin-1a and SNAP-25 with the vesicle SNARE protein synaptobrevin. The neuronal protein Munc18-1 forms a stable complex with syntaxin-1a. Biochemically, syntaxin-1a cannot escape the tight grip of Munc18-1, so formation of the SNARE complex is inhibited. However, Munc18-1 is essential for the release of neurotransmitters in vivo. It has therefore been assumed that Munc18-1 makes the bound syntaxin-1a available for SNARE complex formation. Exactly how this occurs is still unclear, but it is assumed that structural rearrangements occur. Here, we used a series of mutations to specifically weaken the complex at different positions in order to induce these rearrangements biochemically. Our approach was guided through sequence and structural analysis and supported by molecular dynamics simulations. Subsequently, we created a homology model showing the complex in an altered conformation. This conformation presumably represents a more open arrangement of syntaxin-1a that permits the formation of a SNARE complex to be initiated while still bound to Munc18-1. In the future, research should investigate how this central reaction for neuronal communication is controlled by other proteins. This article is protected by copyright. All rights reserved.
Keywords
Munc13, Munc18-1, SM protein, SNARE protein, neuronal secretion, synaptobrevin, syntaxin-1a
Pubmed
Create date
21/12/2023 16:36
Last modification date
22/12/2023 8:50
Usage data