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A search for synthetic peptides that inhibit soluble N ‐ethylmaleimide sensitive‐factor attachment receptor‐mediated membrane fusion
Author(s) -
Jung Chang H.,
Yang YooSoo,
Kim JunSeob,
Shin JaeIl,
Jin YongSu,
Shin Jae Y.,
Lee Jong H.,
Chung Koo M.,
Hwang Jae S.,
Oh Jung M.,
Shin YeonKyun,
Kweon DaeHyuk
Publication year - 2008
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2008.06458.x
Subject(s) - snare complex , lipid bilayer fusion , exocytosis , microbiology and biotechnology , snap25 , membrane , biology , vesicle , vesicle fusion , biophysics , synaptic vesicle , chemistry , biochemistry
Soluble N ‐ethylmaleimide sensitive‐factor attachment receptor (SNARE) proteins have crucial roles in driving exocytic membrane fusion. Molecular recognition between vesicle‐associated (v)‐SNARE and target membrane (t)‐SNARE leads to the formation of a four‐helix bundle, which facilitates the merging of two apposing membranes. Synthetic peptides patterned after the SNARE motifs are predicted to block SNARE complex formation by competing with the parental SNAREs, inhibiting neuronal exocytosis. As an initial attempt to identify the peptide sequences that block SNARE assembly and membrane fusion, we created thirteen 17‐residue synthetic peptides derived from the SNARE motifs of v‐ and t‐SNAREs. The effects of these peptides on SNARE‐mediated membrane fusion were investigated using an in vitro lipid‐mixing assay, in vivo neurotransmitter release and SNARE complex formation assays in PC12 cells. Peptides derived from the N‐terminal region of SNARE motifs had significant inhibitory effects on neuroexocytosis, whereas middle‐ and C‐terminal‐mimicking peptides did not exhibit much inhibitory function. N‐terminal mimicking peptides blocked N‐terminal zippering of SNAREs, a rate‐limiting step in SNARE‐driven membrane fusion. Therefore, the results suggest that the N‐terminal regions of SNARE motifs are excellent targets for the development of drugs to block SNARE‐mediated membrane fusion and neurotransmitter release.