SNARE selectivity of the COPII coat

Area of Science:

• Cell Biology
• Molecular Biology
• Protein-Protein Interactions

Background:

• The COPII (COat Protein complex II) machinery mediates vesicle budding from the endoplasmic reticulum (ER) to the Golgi apparatus.
• Vesicle transport relies on SNARE proteins, which mediate membrane fusion.
• Understanding SNARE recognition by COPII is crucial for elucidating transport specificity.

Purpose of the Study:

• To identify and characterize the binding sites on the yeast COPII Sec23/24 subcomplex responsible for recognizing specific ER-Golgi SNAREs.
• To determine how COPII selects and binds to SNAREs in their functional conformations.

Main Methods:

• Biochemical assays to map binding sites on the Sec23/24 subcomplex.
• Analysis of SNARE motifs and their interactions with COPII.
• Investigating the conformational states of SNAREs during COPII binding.

Main Results:

• Three distinct binding sites (A, B, and a third site) on the Sec23/24 subcomplex were identified for ER-Golgi SNAREs Bet1, Sed5, and Sec22.
• Site A binds the YNNSNPF motif of Sed5; Site B binds Lxx-L/M-E motifs and DxE signals.
• Sec22 binds to a separate site, and COPII selects specific SNARE conformations (free v-SNARE Bet1, t-SNARE complex Sed5) for transport.

Conclusions:

• COPII coat proteins act as specific selectors of fusogenic SNARE conformations.
• This recognition mechanism ensures the fidelity of vesicle budding and targeting from the ER to the Golgi.
• The findings provide insights into the programming of vesicle fusion specificity at the molecular level.