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          Institute: MPI für biophysikalische Chemie     Collection: Neurobiologie (Prof. Reinhard Jahn)     Display Documents



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ID: 17134.0, MPI für biophysikalische Chemie / Neurobiologie (Prof. Reinhard Jahn)
Rapid and selective binding to the synaptic SNARE complex suggests a modulatory role of complexins in neuroexocytosis
Authors:Pabst, S.; Margittai, M.; Vainius, D.; Langen, R.; Jahn, R.; Fasshauer, D.
Language:English
Date of Publication (YYYY-MM-DD):2002-03-08
Title of Journal:Journal of Biological Chemistry
Volume:277
Issue / Number:10
Start Page:7838
End Page:7848
Review Status:Peer-review
Audience:Not Specified
Abstract / Description:The Ca2+ -triggered release of neurotransmitters is mediated by fusion of synaptic vesicles with the plasma membrane. The molecular machinery that translates the Ca2+ signal into exocytosis is only beginning to emerge. The soluble N- ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins syntaxin, SNAP-25, and synaptobrevin are central components of the fusion apparatus. Assembly of a membrane-bridging ternary SNARE complex is thought to initiate membrane merger, but the roles of other factors are less understood. Complexins are two highly conserved proteins that modulate the Ca2+ responsiveness of neurotransmitter release. In vitro, they bind in a 1:1 stoichiometry to the assembled synaptic SNARE complex, making complexins attractive candidates for controlling the exocytotic fusion apparatus. We have now performed a detailed structural, kinetic, and thermodynamic analysis of complexin binding to the SNARE complex. We found that no major conformational changes occur upon binding and that the complexin helix is aligned antiparallel to the four- helix bundle of the SNARE complex. Complexins bound rapidly (approximate to5 X 10(7) M-1 S-1) and with high affinity (approximate to10 nM), making it one of the fastest protein- protein interactions characterized so far in membrane trafficking. Interestingly, neither affinity nor binding kinetics was substantially altered by Ca2+ ions. No interaction of complexins was detectable either with individual SNARE proteins or with the binary syntaxin.SNAP-25 complex. Furthermore, complexin did not promote the formation of SNARE complex oligomers. Together, our data suggest that complexins modulate neuroexocytosis after assembly of membrane-bridging SNARE complexes.
Comment of the Author/Creator:Date: 2002, MAR 8
External Publication Status:published
Document Type:Article
Communicated by:N. N.
Affiliations:MPI für biophysikalische Chemie/Abt. Reinhard Jahn / 190
MPI für biophysikalische Chemie/Abt. Thomas Jovin / 060
MPI für biophysikalische Chemie/AG Dirk Fasshauer
External Affiliations:Univ So Calif, Inst Med Genet, Los Angeles, CA 90033 USA; Univ So Calif, Neurogenet Inst, Dept Biochem & Mol Biol, Los Angeles, CA 90033 USA
Identifiers:URL:http://www.jbc.org/content/277/10/7838.full.pdf+ht...
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