title: The Sec1p/Munc18 protein Vps45p binds its cognate SNARE proteins via two distinct modes.
abstract: Sec1p/Munc18 (SM) proteins are essential for SNARE-mediated membrane trafficking. The formulation of unifying hypotheses for the function of the SM protein family has been hampered by the observation that two of its members bind their cognate syntaxins (Sxs) in strikingly different ways. The SM protein Vps45p binds its Sx Tlg2p in a manner analogous to that captured by the Sly1p-Sed5p crystal structure, whereby the NH2-terminal peptide of the Sx inserts into a hydrophobic pocket on the outer face of domain I of the SM protein. In this study, we report that although this mode of interaction is critical for the binding of Vps45p to Tlg2p, the SM protein also binds Tlg2p-containing SNARE complexes via a second mode that involves neither the NH2 terminus of Tlg2p nor the region of Vps45p that facilitates this interaction. Our findings point to the possibility that SM proteins interact with their cognate SNARE proteins through distinct mechanisms at different stages in the SNARE assembly/disassembly cycle.
authors.affiliation: Henry Wellcome Laboratory of Cell Biology, Division of Biochemistry and Molecular Biology, Faculty of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, Scotland, United Kingdom.
authors.forename: Lindsay N
authors.initials: LN
authors.lastname: Carpp
authors.forename: Leonora F
authors.initials: LF
authors.lastname: Ciufo
authors.forename: Scott G
authors.initials: SG
authors.lastname: Shanks
authors.forename: Alan
authors.initials: A
authors.lastname: Boyd
authors.forename: Nia J
authors.initials: NJ
authors.lastname: Bryant
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D008969:Molecular Sequence Data; D005810:Multigene Family; D051938:Munc18 Proteins / Q000378:metabolism; D009154:Mutation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D050765:Qa-SNARE Proteins / Q000737:chemistry / Q000378:metabolism*; D050683:R-SNARE Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D033921:Vesicular Transport Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D051938:Munc18 Proteins; D050765:Qa-SNARE Proteins; D050683:R-SNARE Proteins; C072520:SLY1 protein, S cerevisiae; C083242:SNC2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C077554:Sed5 protein, S cerevisiae; C112252:TLG2 protein, S cerevisiae; C092934:VPS45 protein, S cerevisiae; D033921:Vesicular Transport Proteins