An electrostatically preferred lateral orientation of SNARE complex suggests novel mechanisms for driving membrane fusion.

PloS One
Ting GuoSen-Fang Sui

Abstract

Biological membrane fusion is a basic cellular process catalyzed by SNARE proteins and additional auxiliary factors. Yet, the critical mechanistic details of SNARE-catalyzed membrane fusion are poorly understood, especially during rapid synaptic transmission. Here, we systematically assessed the electrostatic forces between SNARE complex, auxiliary proteins and fusing membranes by the nonlinear Poisson-Boltzmann equation using explicit models of membranes and proteins. We found that a previously unrecognized, structurally preferred and energetically highly favorable lateral orientation exists for the SNARE complex between fusing membranes. This preferred orientation immediately suggests a novel and simple synaptotagmin-dependent mechanistic trigger of membrane fusion. Moreover, electrostatic interactions between membranes, SNARE complex, and auxiliary proteins appear to orchestrate a series of membrane curvature events that set the stage for rapid synaptic vesicle fusion. Together, our electrostatic analyses of SNAREs and their regulatory factors suggest unexpected and potentially novel mechanisms for eukaryotic membrane fusion proteins.

References

Jan 1, 1990·Annual Review of Biophysics and Biophysical Chemistry·K A Sharp, B Honig
May 26, 1995·Science·B Honig, A Nicholls
Mar 25, 1993·Nature·T SöllnerJ E Rothman
Aug 1, 1995·Current Opinion in Structural Biology·L V Chernomordik, J Zimmerberg
Nov 12, 1996·Proceedings of the National Academy of Sciences of the United States of America·G SchiavoJ E Rothman
Mar 17, 2001·Nature Reviews. Molecular Cell Biology·Y A Chen, R H Scheller
Jun 19, 2001·Proceedings of the National Academy of Sciences of the United States of America·P I KuzminF S Cohen
Aug 23, 2001·Proceedings of the National Academy of Sciences of the United States of America·N A BakerJ A McCammon
Jan 12, 2002·Nature Structural Biology·Wolfram AntoninThomas R Schneider
Jan 24, 2002·Molecular Cell·Diana Murray, Barry Honig
Jan 25, 2002·Biophysical Journal·Yonathan Kozlovsky, Michael M Kozlov
Feb 8, 2002·Neuron·Xiaocheng ChenJosep Rizo
Jul 20, 2002·Trends in Neurosciences·Karla E Marz, Phyllis I Hanson
Nov 5, 2002·Biophysical Journal·Yonathan KozlovskyMichael M Kozlov
Jul 5, 2003·American Journal of Physiology. Cell Physiology·Joseph G Duman, John G Forte
Oct 7, 2003·Annual Review of Biochemistry·Leonid V Chernomordik, Michael M Kozlov
Jan 28, 2004·Cell·Juan S Bonifacino, Benjamin S Glick
Mar 27, 2004·Science·Ward C TuckerEdwin R Chapman
Jun 25, 2004·Nucleic Acids Research·Todd J DolinskyNathan A Baker
Sep 16, 2004·The Journal of Membrane Biology·F S Cohen, G B Melikyan
Jul 6, 2005·Trends in Neurosciences·Jakob B Sørensen
Oct 8, 2005·Journal of Computational Chemistry·David Van Der SpoelHerman J C Berendsen
Nov 4, 2005·Molecular Biology of the Cell·Colin RickmanBazbek Davletov
Mar 28, 2006·Nature Structural & Molecular Biology·Akhil BhallaEdwin R Chapman
May 23, 2006·Nature Structural & Molecular Biology·Joshua ZimmerbergVadim Frolov
Jul 11, 2006·Biochemical and Biophysical Research Communications·Jingguo LiuSen-Fang Sui
Aug 25, 2006·Biochimica Et Biophysica Acta·Anna Mulgrew-NesbittDiana Murray
Oct 18, 2006·The Journal of Cell Biology·Leonid V ChernomordikMichael M Kozlov
Jan 16, 2007·Biophysical Journal·Martin B UlmschneiderAlfredo Di Nola
Feb 27, 2007·Journal of Molecular Biology·Han DaiJosep Rizo
May 5, 2007·Science·Sascha MartensHarvey T McMahon
Jul 3, 2009·Nature·Alexander SteinReinhard Jahn
Oct 22, 2009·Proceedings of the National Academy of Sciences of the United States of America·Anna CypionkaPeter J Walla

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Citations

Jul 20, 2011·Proceedings of the National Academy of Sciences of the United States of America·Kyle D BrewerJosep Rizo
Oct 22, 2011·PloS One·Bradley MooresZoya Leonenko
Jan 20, 2012·Journal of the Royal Society, Interface·Rong LongMaria Bykhovskaia
Sep 1, 2017·Traffic·Tuanlao WangWanjin Hong
Feb 25, 2019·The American Journal of the Medical Sciences·Claudia Carranza, Leslie Chavez-Galan

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Methods Mentioned

BETA
NMR
AFM

Software Mentioned

PDB2PQR
SNARE
Adaptive Poisson - Boltzmann Solver ( APBS
CHARMM
GROMACS

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