Journal article
Low-resolution solution structures of Munc18:Syntaxin protein complexes indicate an open binding mode driven by the Syntaxin N-peptide
MP Christie, AE Whitten, GJ King, SH Hu, RJ Jarrott, KE Chen, AP Duff, P Callow, BM Collins, DE James, JL Martin
Proceedings of the National Academy of Sciences of the United States of America | NATL ACAD SCIENCES | Published : 2012
Abstract
When nerve cells communicate, vesicles from one neuron fuse with the presynaptic membrane releasing chemicals that signal to the next. Similarly, when insulin binds its receptor on adipocytes or muscle, glucose transporter-4 vesicles fuse with the cell membrane, allowing glucose to be imported. These essential processes require the interaction of SNARE proteins on vesicle and cell membranes, as well as the enigmatic protein Munc18 that binds the SNARE protein Syntaxin. Here, we show that in solution the neuronal protein Syntaxin1a interacts with Munc18-1 whether or not the Syntaxin1a N-peptide is present. Conversely, the adipocyte protein Syntaxin4 does not bind its partner Munc18c unless th..
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Awarded by National Health and Medical Research Council (NHMRC)
Awarded by Australian Government
Funding Acknowledgements
We thank Jill Trewhella, Kevin Jack, and Nathan Cowieson for help with SAXS and Alun Jones for mass spectrometric measurements. This work was supported by National Health and Medical Research Council (NHMRC) Program 535921. A.E.W. is an NHMRC Peter Doherty Fellow (569864); B.M.C. is an Australian Research Council (ARC) Future Fellow (FT100100027), D.E.J. is an NHMRC Senior Principal Research Fellow (1019680), and J.L.M. is an ARC Australian Laureate Fellow (FL0992138) and honorary NHMRC Fellow (455829). Protein deuteration at the National Deuteration Facility was partly funded by the National Collaborative Research Infrastructure Strategy of the Australian Government. Recombinant expression of Munc18c was performed at the University of Queensland Protein Expression Facility. We also acknowledge financial support from the Access to Major Research Facilities Program of the Australian Government (08/09-N-47) and access to the SAXS/WAXS beamline at the Australian Synchrotron.