Low-resolution solution structures of Munc18:Syntaxin protein complexes indicate an open binding mode driven by the Syntaxin N-peptide

Simple item page
dc.contributor.authorChristie, MPen_AU
dc.contributor.authorWhitten, AEen_AU
dc.contributor.authorKing, GJen_AU
dc.contributor.authorHu, SHen_AU
dc.contributor.authorJarrott, RJen_AU
dc.contributor.authorChen, KEen_AU
dc.contributor.authorDuff, APen_AU
dc.contributor.authorCallow, Pen_AU
dc.contributor.authorCollins, BMen_AU
dc.contributor.authorJames, DEen_AU
dc.contributor.authorMartin, JLen_AU
dc.date.accessioned2014-04-17T05:34:09Zen_AU
dc.date.available2014-04-17T05:34:09Zen_AU
dc.date.issued2012-06-19en_AU
dc.date.statistics2014-04-17en_AU
dc.description.abstractWhen 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 the N-peptide is present. Solution-scattering data for the Munc18-1:Syntaxin1a complex in the absence of the N-peptide indicates that this complex adopts the inhibitory closed binding mode, exemplified by a crystal structure of the complex. However, when the N-peptide is present, the solution-scattering data indicate both Syntaxin1a and Syntaxin4 adopt extended conformations in complexes with their respective Munc18 partners. The low-resolution solution structure of the open Munc18:Syntaxin binding mode was modeled using data from cross-linking/mass spectrometry, small-angle X-ray scattering, and small-angle neutron scattering with contrast variation, indicating significant differences in Munc18:Syntaxin interactions compared with the closed binding mode. Overall, our results indicate that the neuronal Munc18-1:Syntaxin1a proteins can adopt two alternate and functionally distinct binding modes, closed and open, depending on the presence of the N-peptide, whereas Munc18c:Syntaxin4 adopts only the open binding mode. © 2012, National Academy of Sciences.en_AU
dc.identifier.citationChristie, M. P., Whitten, A. E., King, G. J., Hu, S. H., Jarrott, R. J., Chen, K. E., Duff, A. P., Callow, P., Collins, B. M., James, D. E., & Martin, J. L. (2012). Low-resolution solution structures of Munc18:Syntaxin protein complexes indicate an open binding mode driven by the Syntaxin N-peptide. Proceedings of the National Academy of Sciences, 109(25), 9816-9821. doi:10.1073/pnas.1116975109en_AU
dc.identifier.govdoc4661en_AU
dc.identifier.issn1091-6490en_AU
dc.identifier.issue25en_AU
dc.identifier.journaltitleProceedings of the National Academy of Sciencesen_AU
dc.identifier.pagination9816-9821en_AU
dc.identifier.urihttp://dx.doi.org/10.1073/pnas.1116975109en_AU
dc.identifier.urihttp://apo.ansto.gov.au/dspace/handle/10238/5452en_AU
dc.identifier.volume109en_AU
dc.language.isoenen_AU
dc.publisherNational Academy of Sciencesen_AU
dc.subjectCell membranesen_AU
dc.subjectMembrane proteinsen_AU
dc.subjectProteinsen_AU
dc.subjectSmall angle scatteringen_AU
dc.subjectPeptidesen_AU
dc.subjectMass spectroscopyen_AU
dc.titleLow-resolution solution structures of Munc18:Syntaxin protein complexes indicate an open binding mode driven by the Syntaxin N-peptideen_AU
dc.typeJournal Articleen_AU
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
9816.full.pdf
Size:
591.93 KB
Format:
Adobe Portable Document Format
Description:
Download
License bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
license.txt
Size:
1.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Journal Articles