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Title: Complexin cross-links prefusion SNAREs into a zigzag array

Abstract

Complexin prevents SNAREs from releasing neurotransmitters until an action potential arrives at the synapse. To understand the mechanism for this inhibition, we determined the structure of complexin bound to a mimetic of a prefusion SNAREpin lacking the portion of the v-SNARE that zippers last to trigger fusion. The 'central helix' of complexin is anchored to one SNARE complex, while its 'accessory helix' extends away at {approx}45 deg. and bridges to a second complex, occupying the vacant v-SNARE binding site to inhibit fusion. We expected the accessory helix to compete with the v-SNARE for t-SNARE binding but found instead that the interaction occurs intermolecularly. Thus, complexin organizes the SNAREs into a zigzag topology that, when interposed between the vesicle and plasma membranes, is incompatible with fusion.

Authors:
; ; ; ; ; ; ;  [1]
  1. (Yale-MED)
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
FOREIGNNIH
OSTI Identifier:
1023675
Resource Type:
Journal Article
Journal Name:
Nat. Struct. Mol. Biol.
Additional Journal Information:
Journal Volume: 18; Journal Issue: 2011
Country of Publication:
United States
Language:
ENGLISH
Subject:
60 APPLIED LIFE SCIENCES; CELL MEMBRANES; INHIBITION; INTERACTIONS; MEMBRANES; PLASMA; POTENTIALS

Citation Formats

Kümmel, Daniel, Krishnakumar, Shyam S., Radoff, Daniel T., Li, Feng, Giraudo, Claudio G., Pincet, Frederic, Rothman, James E., and Reinisch, Karin M. Complexin cross-links prefusion SNAREs into a zigzag array. United States: N. p., 2011. Web. doi:10.1038/nsmb.2101.
Kümmel, Daniel, Krishnakumar, Shyam S., Radoff, Daniel T., Li, Feng, Giraudo, Claudio G., Pincet, Frederic, Rothman, James E., & Reinisch, Karin M. Complexin cross-links prefusion SNAREs into a zigzag array. United States. doi:10.1038/nsmb.2101.
Kümmel, Daniel, Krishnakumar, Shyam S., Radoff, Daniel T., Li, Feng, Giraudo, Claudio G., Pincet, Frederic, Rothman, James E., and Reinisch, Karin M. Tue . "Complexin cross-links prefusion SNAREs into a zigzag array". United States. doi:10.1038/nsmb.2101.
@article{osti_1023675,
title = {Complexin cross-links prefusion SNAREs into a zigzag array},
author = {Kümmel, Daniel and Krishnakumar, Shyam S. and Radoff, Daniel T. and Li, Feng and Giraudo, Claudio G. and Pincet, Frederic and Rothman, James E. and Reinisch, Karin M.},
abstractNote = {Complexin prevents SNAREs from releasing neurotransmitters until an action potential arrives at the synapse. To understand the mechanism for this inhibition, we determined the structure of complexin bound to a mimetic of a prefusion SNAREpin lacking the portion of the v-SNARE that zippers last to trigger fusion. The 'central helix' of complexin is anchored to one SNARE complex, while its 'accessory helix' extends away at {approx}45 deg. and bridges to a second complex, occupying the vacant v-SNARE binding site to inhibit fusion. We expected the accessory helix to compete with the v-SNARE for t-SNARE binding but found instead that the interaction occurs intermolecularly. Thus, complexin organizes the SNAREs into a zigzag topology that, when interposed between the vesicle and plasma membranes, is incompatible with fusion.},
doi = {10.1038/nsmb.2101},
journal = {Nat. Struct. Mol. Biol.},
number = 2011,
volume = 18,
place = {United States},
year = {2011},
month = {9}
}