Cog5-Cog7 crystal structure reveals interactions essential for the function of a multisubunit tethering complex

Area of Science:

• Cell biology
• Molecular biology
• Structural biology

Background:

• The conserved oligomeric Golgi (COG) complex is crucial for vesicle docking and fusion at the Golgi apparatus.
• COG acts as a scaffold, directing SNARE complex assembly for membrane fusion.
• Mutations in COG cause congenital disorders of glycosylation, highlighting its importance.

Purpose of the Study:

• To elucidate the molecular structure of the COG complex, particularly its less-understood lobe B subunits.
• To investigate the structural basis of COG function and its role in Golgi trafficking and glycosylation.

Main Methods:

• Crystal structure determination of the Cog5-Cog7 complex.
• Bioinformatic analysis of Cog5 homology to other multisubunit tethering complex (MTC) proteins.
• Biochemical and functional assays to validate the Cog5-Cog7 interaction and its physiological relevance.

Main Results:

• The crystal structure of the Cog5-Cog7 complex was determined, revealing Cog5 belongs to the CATCHR fold family.
• The Cog5-Cog7 interaction shares similarities with the Dsl1 complex, another CATCHR-family MTC.
• Disruption of the Cog5-Cog7 interface in human cells led to impaired trafficking and glycosylation.

Conclusions:

• The Cog5-Cog7 structure provides insights into COG complex assembly and function.
• The conserved Cog5-Cog7 interaction is vital for Golgi trafficking and glycosylation.
• Understanding COG subunit interactions is key to deciphering its role in health and disease.