The ionic layer is required for efficient dissociation of the SNARE complex by alpha-SNAP and NSF.

Abstract:

:The four-helical bundle soluble N-ethylmaleimide-sensitive fusion protein (NSF) attachment protein receptor (SNARE) complex that mediates intracellular membrane fusion events contains a highly conserved ionic layer at the center of an otherwise hydrophobic core. This layer has an undetermined function; it consists of glutamine (Q) residues in syntaxin and the two synaptosomal-associated protein of 25 kDa (SNAP-25) family helices, and an arginine (R) in vesicle-associated membrane protein (a 3Q:1R ratio). Here, we show that the ionic-layer glutamine of syntaxin is required for efficient alpha-SNAP and NSF-mediated dissociation of the complex. When this residue is mutated, the SNARE complex still binds to alpha-SNAP and NSF and is released through ATP hydrolysis by NSF, but the complex no longer dissociates into SNARE monomers. Thus, one function of the ionic layer--in particular, the glutamine of syntaxin--is to couple ATP hydrolysis by NSF to the dissociation of the fusion complex. We propose that alpha-SNAP and NSF drive conformational changes at the ionic layer through specific interactions with the syntaxin glutamine, resulting in the dissociation of the SNARE complex.

authors

Scales SJ,Yoo BY,Scheller RH

doi

10.1073/pnas.251547598

keywords:

subject

Has Abstract

pub_date

2001-12-04 00:00:00

pages

14262-7

issue

25

eissn

0027-8424

issn

1091-6490

journal_volume

98

pub_type

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