title: Cellular levels of the syntaxin Tlg2p are regulated by a single mode of binding to Vps45p.
abstract: Sec1p/Munc18 (SM) proteins play a key role in the regulation of soluble N-ethylmaleimide-sensitive fusion (NSF)-attachment protein receptor (SNARE)-mediated intracellular membrane trafficking events in all eukaryotic cells. Understanding the molecular mechanisms by which SM proteins function has not been straight forward as SM proteins bind to their cognate SNARE proteins by at least two distinct mechanisms, suggesting that they provide more than one function. We have previously characterised two binding modes used by the yeast SM protein Vps45p to interact with its SNARE proteins. In one of these modes, the N terminus of the syntaxin Tlg2p inserts into a hydrophobic pocket in the SM protein. We now report that disruption of this high-affinity binding between Vps45p and Tlg2p leads to downregulation of Tlg2p, and propose that this pocket-mode of binding of SM proteins to their cognate syntaxins serves to regulate cellular levels of the syntaxin.
authors: Henry Wellcome Laboratory of Cell Biology, Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, University of Glasgow, Davidson Building, Glasgow G12 8QQ, UK.
authors: Lindsay N
authors: LN
authors: Carpp
authors: Scott G
authors: SG
authors: Shanks
authors: Marion S
authors: MS
authors: Struthers
authors: Nia J
authors: NJ
authors: Bryant
mesh_terms: D001667:Binding, Competitive; D015536:Down-Regulation; D015151:Immunoblotting; D009154:Mutation; D011485:Protein Binding; D050765:Qa-SNARE Proteins / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D050765:Qa-SNARE Proteins; D029701:Saccharomyces cerevisiae Proteins; C112252:TLG2 protein, S cerevisiae; C092934:VPS45 protein, S cerevisiae; D033921:Vesicular Transport Proteins