Journal article
Possible roles for Munc18-1 domain 3a and Syntaxin1 N-peptide and C-terminal anchor in SNARE complex formation
SH Hu, MP Christie, NJ Saez, CF Latham, R Jarrott, LHL Lua, BM Collins, JL Martin
Proceedings of the National Academy of Sciences of the United States of America | NATL ACAD SCIENCES | Published : 2011
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..
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Awarded by Australian National Health and Medical Research Council (NHMRC)
Funding Acknowledgements
We thank Jingshi Shen for the Munc18-1-His clone, Fred Meunier for critical comment, and the Australian National Health and Medical Research Council (NHMRC) for financial support (Grants 401643 and 535921). J.L.M. is an Australian Research Council Laureate Fellow and Honorary NHMRC Fellow; B.M.C. holds an NHMRC Career Development Award. We acknowledge use of the University of Queensland Remote Operation Crystallization and X-ray Diffraction Facility and thank Karl Byriel and Gordon King for assistance. X-ray data were measured on the MX2 beamline at the Australian Synchrotron, Victoria, Australia.