Possible roles for Munc18-1 domain 3a and Syntaxin1 N-peptide and C-terminal anchor in SNARE complex formation

Hu, Shu-Hong, Christie, Michelle P., Saez, Natalie J., Latham, Catherine F., Jarrott, Russell, Lua, Linda H. L., Collins, Brett M. and Martin, Jennifer L. (2011) Possible roles for Munc18-1 domain 3a and Syntaxin1 N-peptide and C-terminal anchor in SNARE complex formation. Proceedings of the National Academy of Sciences of the United States of America, 108 3: 1040-1045. doi:10.1073/pnas.0914906108


Author Hu, Shu-Hong
Christie, Michelle P.
Saez, Natalie J.
Latham, Catherine F.
Jarrott, Russell
Lua, Linda H. L.
Collins, Brett M.
Martin, Jennifer L.
Title Possible roles for Munc18-1 domain 3a and Syntaxin1 N-peptide and C-terminal anchor in SNARE complex formation
Journal name Proceedings of the National Academy of Sciences of the United States of America   Check publisher's open access policy
ISSN 0027-8424
1091-6490
Publication date 2011-01-18
Year available 2010
Sub-type Article (original research)
DOI 10.1073/pnas.0914906108
Open Access Status Not Open Access
Volume 108
Issue 3
Start page 1040
End page 1045
Total pages 6
Place of publication Washington, DC, United States
Publisher National Academy of Sciences
Collection year 2011
Language eng
Abstract Munc18-1 and Syntaxin1 are essential proteins for SNARE-mediated neurotransmission. Munc18-1 participates in synaptic vesicle fusion via dual roles: as a docking/chaperone protein by binding closed Syntaxin1, and as a fusion protein that binds SNARE complexes in a Syntaxin1 N-peptide dependent manner. The two roles are associated with a closed-open Syntaxin1 conformational transition. Here, we show that Syntaxin N-peptide binding to Munc18-1 is not highly selective, suggesting that other parts of the SNARE complex are involved in binding to Munc18-1. We also find that Syntaxin1, with an N peptide and a physically anchored C terminus, binds to Munc18-1 and that this complex can participate in SNARE complex formation. We report a Munc18-1-N-peptide crystal structure that, together with other data, reveals how Munc18-1 might transit from a conformation that binds closed Syntaxin1 to one that may be compatible with binding open Syntaxin1 and SNARE complexes. Our results suggest the possibility that structural transitions occur in both Munc18-1 and Syntaxin1 during their binary interaction. We hypothesize that Munc18-1 domain 3a undergoes a conformational change that may allow coiled-coil interactions with SNARE complexes.
Keyword Membrane trafficking
Protein-peptide interaction
Protein-protein interaction
Sec/Munc protein
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online before print December 30, 2010,

 
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Created: Sun, 27 Feb 2011, 00:02:03 EST