SNARE selectivity of the COPII coat.
The COPII coat buds transport vesicles from the endoplasmic reticulum that incorporate cargo and SNARE molecules. Here, we show that recognition of the ER-Golgi SNAREs Bet1, Sed5, and Sec22 occurs through three binding sites on the Sec23/24 subcomplex of yeast COPII. The A site binds to the YNNSNPF motif of Sed5. The B site binds to Lxx-L/M-E sequences present in both the Bet1 and Sed5 molecules, as well as to the DxE cargo-sorting signal. A third, spatially distinct site binds to Sec22. COPII selects the free v-SNARE form of Bet1 because the LxxLE sequence is sequestered in the four-helix bundle of the v-/t-SNARE complex. COPII favors Sed5 within the Sed5/Bos1/Sec22 t-SNARE complex because t-SNARE assembly removes autoinhibitory contacts to expose the YNNSNPF motif. The COPII coat seems to be a specific conductor of the fusogenic forms of these SNAREs, suggesting how vesicle fusion specificity may be programmed during budding.
Mossessova
Elena
E
Howard Hughes Medical Institute and the Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
Bickford
Lincoln C
LC
Goldberg
Jonathan
J
D020816:Amino Acid Motifs; D022181:COP-Coated Vesicles / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018360:Crystallography, X-Ray; D020690:GTPase-Activating Proteins; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000502:physiology; D050765:Qa-SNARE Proteins; D050767:Qc-SNARE Proteins; D050683:R-SNARE Proteins; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D050600:SNARE Proteins; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity; D033921:Vesicular Transport Proteins
C107845:BET1 protein, S cerevisiae; D002352:Carrier Proteins; D020690:GTPase-Activating Proteins; D046911:Macromolecular Substances; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D010750:Phosphoproteins; D050765:Qa-SNARE Proteins; D050767:Qc-SNARE Proteins; D050683:R-SNARE Proteins; D011956:Receptors, Cell Surface; C079037:SEC23 protein, S cerevisiae; C106113:SEC31 protein, S cerevisiae; D050600:SNARE Proteins; D029701:Saccharomyces cerevisiae Proteins; C106909:Sec22 protein, S cerevisiae; C077554:Sed5 protein, S cerevisiae; D033921:Vesicular Transport Proteins