How Tlg2p/syntaxin 16 'snares' Vps45.
Soluble N-ethylmaleimide sensitive factor-attachment protein receptors (SNAREs) and Sec1p/Munc18-homologs (SM proteins) play key roles in intracellular membrane fusion. The SNAREs form tight four-helix bundles (core complexes) that bring the membranes together, but it is unclear how this activity is coupled to SM protein function. Studies of the yeast trans-Golgi network (TGN)/endosomal SNARE complex, which includes the syntaxin-like SNARE Tlg2p, have suggested that its assembly requires activation by binding of the SM protein Vps45p to the cytoplasmic region of Tlg2p folded into a closed conformation. Nuclear magnetic resonance and biochemical experiments now show that Tlg2p and Pep12p, a late- endosomal syntaxin that interacts functionally but not directly with Vps45p, have a domain structure characteristic of syntaxins but do not adopt a closed conformation. Tlg2p binds tightly to Vps45p via a short N-terminal peptide motif that is absent in Pep12p. The Tlg2p/Vps45p binding mode is shared by the mammalian syntaxin 16, confirming that it is a Tlg2p homolog, and resembles the mode of interaction between the SM protein Sly1p and the syntaxins Ufe1p and Sed5p. Thus, this mechanism represents the most widespread mode of coupling between syntaxins and SM proteins.
Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
Irina
I
Dulubova
Tomohiro
T
Yamaguchi
Yan
Y
Gao
Sang-Won
SW
Min
Iryna
I
Huryeva
Thomas C
TC
Südhof
Josep
J
Rizo
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D005656:Fungal Proteins / Q000737:chemistry / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D050765:Qa-SNARE Proteins; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D051438:Syntaxin 16; D033921:Vesicular Transport Proteins
D005656:Fungal Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D050765:Qa-SNARE Proteins; D029701:Saccharomyces cerevisiae Proteins; D051438:Syntaxin 16; C112252:TLG2 protein, S cerevisiae; C092934:VPS45 protein, S cerevisiae; D033921:Vesicular Transport Proteins