Munc18-1 induces conformational changes of syntaxin-1 in multiple intermediates for SNARE assembly.

Scientific Reports
Sanghwa LeeYeon-Kyun Shin

Abstract

In neuronal exocytosis, SNARE assembly into a stable four-helix bundle drives membrane fusion. Previous studies have revealed that the SM protein Munc18-1 plays a critical role for precise SNARE assembly with the help of Munc13-1, but the underlying mechanism remains unclear. Here, we used single-molecule FRET assays with a nanodisc membrane reconstitution system to investigate the conformational dynamics of SNARE/Munc18-1 complexes in multiple intermediate steps towards the SNARE complex. We found that single Munc18-1 proteins induce the closed conformation of syntaxin-1 not only in the free syntaxin-1 but also in the t-SNARE (syntaxin-1/SNAP-25) complex. These results implicate that Munc18-1 may act as a gatekeeper for both binary and ternary SNARE complex formation by locking the syntaxin-1 in a cleft of Munc18-1. Furthermore, the kinetic analysis of the opening/closing transition reveals that the closed syntaxin-1 in the syntaxin-1/SNAP-25/Munc18-1 complex is less stable than that in the closed syntaxin-1/Munc18-1 complex, which is manifested by the infrequent closing transition, indicating that the conformational equilibrium of the ternary complex is biased toward the open conformation of syntaxin-1 compared with the binar...Continue Reading

References

Sep 10, 1998·Nature Structural Biology·M A PoirierM K Bennett
Jan 29, 2000·The Journal of Cell Biology·B YangR H Scheller
Dec 12, 2003·Proceedings of the National Academy of Sciences of the United States of America·M MargittaiC A M Seidel
Aug 17, 2006·Nature Reviews. Molecular Cell Biology·Reinhard Jahn, Richard H Scheller
Oct 3, 2006·Nature Methods·Ivan RasnikTaekjip Ha
Jan 16, 2007·Cell·Jingshi ShenThomas J Melia
Feb 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Irina DulubovaJosep Rizo
Oct 25, 2007·Trends in Neurosciences·Ruud F G Toonen, Matthijs Verhage
Mar 14, 2008·The EMBO Journal·Pawel BurkhardtDirk Fasshauer
May 31, 2008·Nature Methods·Rahul RoyTaekjip Ha
Jul 12, 2008·Nature Structural & Molecular Biology·Josep Rizo, Christian Rosenmund
Oct 3, 2008·Molecular Biology of the Cell·Travis L RodkeyJames A McNew
Jan 24, 2009·Science·Thomas C Südhof, James E Rothman
Dec 8, 2010·Proceedings of the National Academy of Sciences of the United States of America·Yoosoo YangDae-Hyuk Kweon
Apr 19, 2011·Nature Structural & Molecular Biology·Cong MaJosep Rizo
Oct 13, 2012·Annual Review of Cell and Developmental Biology·Josep Rizo, Thomas C Südhof
Oct 13, 2012·Nature·Reinhard Jahn, Dirk Fasshauer
Feb 27, 2015·The Journal of Biological Chemistry·Xiaochu LouYeon-Kyun Shin
Jun 2, 2015·Nature Structural & Molecular Biology·Xiaoyu YangCong Ma
Jun 23, 2015·Annual Review of Biophysics·Josep Rizo, Junjie Xu
Feb 16, 2016·Structure·Damian Dawidowski, David S Cafiso
Jun 16, 2016·Nature Reviews. Molecular Cell Biology·Richard W Baker, Frederick M Hughson
May 10, 2017·The EMBO Journal·Shrutee JakhanwalReinhard Jahn
Jan 1, 2020·Proceedings of the National Academy of Sciences of the United States of America·Tong ShuYongli Zhang

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Methods Mentioned

BETA
fluorescence resonance
FRET
electron paramagnetic resonance

Software Mentioned

MATLAB
IDL ITT Visual Information Solutions

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