Architecture of the Synaptophysin/Synaptobrevin Complex: Structural Evidence for an Entropic Clustering Function at the Synapse

Scientific Reports
Daniel J AdamsMichael H B Stowell

Abstract

We have purified the mammalian synaptophysin/synaptobrevin (SYP/VAMP2) complex to homogeneity in the presence of cholesterol and determined the 3D EM structure by single particle reconstruction. The structure reveals that SYP and VAMP2 assemble into a hexameric ring wherein 6 SYP molecules bind 6 VAMP2 dimers. Using the EM map as a constraint, a three dimensional atomic model was built and refined using known atomic structures and homology modeling. The overall architecture of the model suggests a simple mechanism to ensure cooperativity of synaptic vesicle fusion by organizing multiple VAMP2 molecules such that they are directionally oriented towards the target membrane. This is the first three dimensional architectural data for the SYP/VAMP2 complex and provides a structural foundation for understanding the role of this complex in synaptic transmission.

References

Oct 1, 1985·Analytical Biochemistry·P K SmithD C Klenk
Jun 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·R JahnP Greengard
Dec 1, 1995·Cell and Tissue Research·L G Eshkind, R E Leube
Nov 14, 1996·Nature·B L Sabatini, W G Regehr
Dec 22, 1999·Journal of Structural Biology·S J LudtkeW Chiu
Dec 24, 2002·Biophysical Journal·Dan Gincel, Varda Shoshan-Barmatz
May 16, 2006·Proceedings of the National Academy of Sciences of the United States of America·Christian AbrahamRudolf E Leube
Nov 18, 2006·Cell·Shigeo TakamoriReinhard Jahn
Jun 15, 2007·Structure·Christopher P Arthur, Michael H B Stowell
Aug 21, 2007·Cell Biology International·Won Jin ChoBhanu P Jena
Aug 25, 2007·Science·Jochen J SieberThorsten Lang
Mar 3, 2009·Proceedings of the National Academy of Sciences of the United States of America·Jiansong TongYeon-Kyun Shin
Apr 3, 2009·Nature·Shoji MaedaTomitake Tsukihara
Apr 21, 2009·Nature Genetics·Patrick S TarpeyMichael R Stratton
Nov 18, 2009·Proceedings of the National Academy of Sciences of the United States of America·Jeffrey F EllenaLukas K Tamm
Nov 20, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Christian Tackenberg, Roland Brandt
Feb 6, 2010·Proceedings of the National Academy of Sciences of the United States of America·Erdem KaratekinJames E Rothman
Feb 9, 2010·Nature Structural & Molecular Biology·Geert van den BogaartReinhard Jahn
Apr 29, 2010·Current Neurology and Neuroscience Reports·Myrrhe van Spronsen, Casper C Hoogenraad
Sep 18, 2010·Science·Ralf MohrmannJakob B Sørensen
Sep 21, 2010·Trends in Neurosciences·Austen J Milnerwood, Lynn A Raymond
Oct 1, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Sarah L GordonMichael A Cousin
May 15, 2013·Biophysical Journal·Volker KiesslingLukas K Tamm
Aug 24, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Sarah L Gordon, Michael A Cousin

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Citations

Feb 24, 2016·Frontiers in Synaptic Neuroscience·Sarah L Gordon, Michael A Cousin
May 25, 2018·Annual Review of Biophysics·Axel T BrungerQiangjun Zhou
Jun 29, 2018·The EMBO Journal·Sven TruckenbrodtSilvio O Rizzoli
Feb 9, 2017·The Journal of General Physiology·Che-Wei ChangMeyer B Jackson
Jan 31, 2018·Frontiers in Cellular Neuroscience·Yasunori Mori, Shigeo Takamori
Feb 9, 2017·Annals of Clinical and Translational Neurology·Xin-Ming ShenAndrew G Engel
May 28, 2019·Scientific Reports·Katharina J Seitz, Silvio O Rizzoli
Oct 27, 2017·Frontiers in Molecular Neuroscience·Zhenyong WuErdem Karatekin
Oct 8, 2020·International Journal of Molecular Sciences·Sofiia ReshetniakChristian Tetzlaff
Jan 21, 2021·Proceedings of the National Academy of Sciences of the United States of America·Abhijith RadhakrishnanJames E Rothman
Mar 27, 2021·The Journal of Biological Chemistry·Callista B HarperMichael A Cousin

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Methods Mentioned

BETA
electron microscopy
NMR
gel filtration

Software Mentioned

CHIMERA
ImageJ
ExPASy ProtScale
Paralog
PSI
EMAN2
AlignMe
MaxSprout
PRALINE
ClustalW

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