title: The SM protein Sly1 accelerates assembly of the ER-Golgi SNARE complex.
abstract: Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) and Sec1/Munc18 (SM) proteins constitute the core of an ancient vesicle fusion machine that diversified into distinct sets that now function in different trafficking steps in eukaryotic cells. Deciphering their precise mode of action has proved challenging. SM proteins are thought to act primarily through one type of SNARE protein, the syntaxins. Despite high structural similarity, however, contrasting binding modes have been found for different SM proteins and syntaxins. Whereas the secretory SM protein Munc18 binds to the ‟closed conformation" of syntaxin 1, the ER-Golgi SM protein Sly1 interacts only with the N-peptide of Sed5. Recent findings, however, indicate that SM proteins might interact simultaneously with both syntaxin regions. In search for a common mechanism, we now reinvestigated the Sly1/Sed5 interaction. We found that individual Sed5 adopts a tight closed conformation. Sly1 binds to both the closed conformation and the N-peptide of Sed5, suggesting that this is the original binding mode of SM proteins and syntaxins. In contrast to Munc18, however, Sly1 facilitates SNARE complex formation by loosening the closed conformation of Sed5.
authors.affiliation: Research Group Structural Biochemistry, Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany; and.
authors.forename: F Esra
authors.initials: FE
authors.lastname: Demircioglu
authors.affiliation: Research Group Structural Biochemistry, Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany; and.
authors.forename: Pawel
authors.initials: P
authors.lastname: Burkhardt
authors.affiliation: Research Group Structural Biochemistry, Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany; and Department of Fundamental Neurosciences, University of Lausanne, 1005 Lausanne, Switzerland Dirk.Fasshauer@unil.ch.
authors.forename: Dirk
authors.initials: D
authors.lastname: Fasshauer
mesh_terms: D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism*; D006056:Golgi Apparatus / Q000235:genetics / Q000378:metabolism*; D051938:Munc18 Proteins / Q000235:genetics / Q000378:metabolism*; 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*
chemical_list: D051938:Munc18 Proteins; D050765:Qa-SNARE Proteins; C072520:SLY1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C077554:Sed5 protein, S cerevisiae
keywords: ER–Golgi trafficking; fluorescence spectroscopy; isothermal titration calorimetry; membrane fusion; protein–protein interaction