title: Characterization of two distinct binding modes between syntaxin 4 and Munc18c.
abstract: Interaction of SM (Sec1/Munc18) proteins with their cognate syntaxins represents an important regulatory mechanism of SNARE (soluble N-ethylmaleimide-sensitive fusion protein-attachment protein receptor)-mediated membrane fusion. Understanding the conserved mechanisms by which SM proteins function in this process has proved challenging, largely due to an apparent lack of conservation of binding mechanisms between different SM-syntaxin pairs. In the present study, we have identified a hitherto uncharacterized mode of binding between syntaxin 4 and Munc18c that is independent of the binding mode shown previously to utilize the N-terminal peptide of syntaxin 4. Our data demonstrate that syntaxin 4 and Munc18c interact via two distinct modes of binding, analogous to those employed by syntaxin 1a-Munc18a and syntaxin 16-Vps45p (vacuolar protein sorting 45). These data support the notion that all syntaxin/SM proteins bind using conserved mechanisms, and pave the way for the formulation of unifying hypotheses of SM protein function.
authors.affiliation: Henry Wellcome Laboratory of Cell Biology, Division of Molecular and Cellular Biology, Davidson Building, Faculty of Biomedical and Life Science, University of Glasgow, Glasgow, U.K.
authors.forename: Veronica
authors.initials: V
authors.lastname: Aran
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Brandie
authors.forename: Alasdair R
authors.initials: AR
authors.lastname: Boyd
authors.forename: Theodoros
authors.initials: T
authors.lastname: Kantidakis
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Rideout
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Kelly
authors.forename: Gwyn W
authors.initials: GW
authors.lastname: Gould
authors.forename: Nia J
authors.initials: NJ
authors.lastname: Bryant
mesh_terms: D000818:Animals; D051938:Munc18 Proteins / Q000378:metabolism*; D050505:Mutant Proteins / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism; D011485:Protein Binding; D050765:Qa-SNARE Proteins / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism
chemical_list: D051938:Munc18 Proteins; D050505:Mutant Proteins; D050765:Qa-SNARE Proteins; D011993:Recombinant Fusion Proteins; D010447:Peptide Hydrolases