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

Journal Article


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.

UOW Authors


  •   Hu, Shu-Hong (external author)
  •   Christie, Michelle P. (external author)
  •   Saez, Natalie (external author)
  •   Latham, Catherine (external author)
  •   Jarrott, Russell J. (external author)
  •   Lua, Linda (external author)
  •   Collins, Brett M. (external author)
  •   Martin, Jennifer (external author)

Publication Date


  • 2011

Citation


  • Hu, S., Christie, M. P., Saez, N. J., Latham, C. F., Jarrott, R., Lua, L. H. L., Collins, B. M. & Martin, J. 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.

Scopus Eid


  • 2-s2.0-79551637409

Number Of Pages


  • 5

Start Page


  • 1040

End Page


  • 1045

Volume


  • 108

Issue


  • 3

Place Of Publication


  • United States

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.

UOW Authors


  •   Hu, Shu-Hong (external author)
  •   Christie, Michelle P. (external author)
  •   Saez, Natalie (external author)
  •   Latham, Catherine (external author)
  •   Jarrott, Russell J. (external author)
  •   Lua, Linda (external author)
  •   Collins, Brett M. (external author)
  •   Martin, Jennifer (external author)

Publication Date


  • 2011

Citation


  • Hu, S., Christie, M. P., Saez, N. J., Latham, C. F., Jarrott, R., Lua, L. H. L., Collins, B. M. & Martin, J. 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.

Scopus Eid


  • 2-s2.0-79551637409

Number Of Pages


  • 5

Start Page


  • 1040

End Page


  • 1045

Volume


  • 108

Issue


  • 3

Place Of Publication


  • United States