Structural basis for the binding of SNAREs to the multisubunit tethering complex Dsl1

Area of Science:

• Cell biology
• Molecular biology
• Structural biology

Background:

• Multisubunit-tethering complexes (MTCs) are essential for SNARE-mediated membrane fusion.
• MTCs organize membrane trafficking by facilitating initial vesicle-target membrane interactions.
• The yeast Dsl1 complex, a simple MTC, is vital for COPI-mediated transport between the Golgi and ER.

Purpose of the Study:

• To investigate the structural basis of Dsl1 complex interactions with ER-associated SNAREs.
• To elucidate the role of these interactions in tethering and SNARE complex formation.

Main Methods:

• X-ray crystallography was employed to determine the structure of the Dsl1 complex bound to ER SNAREs.
• Analysis of the binding interfaces between Dsl1 subunits and SNARE N-terminal domains.

Main Results:

• The Dsl1 complex, with its two-legged structure, binds the N-terminal Habc domains of ER SNAREs Sec20 (Qb-SNARE) and Use1 (Qc-SNARE).
• These interactions anchor the complex to the ER membrane and maintain SNAREs in an open, accessible conformation for assembly.
• The relative orientation of Dsl1 legs influences the proximity of SNARE motifs for complex formation.

Conclusions:

• The N-terminal domains of SNAREs play a critical role in mediating interactions with tethering machinery.
• Dsl1 complex binding to SNAREs facilitates vesicle tethering and promotes SNARE complex assembly for membrane fusion.
• Structural insights into Dsl1-SNARE interactions provide a framework for understanding COPI-mediated transport.