Cog5-Cog7 crystal structure reveals interactions essential for the function of a multisubunit tethering complex. Author Jun Ha, Irina Pokrovskaya, Leslie Climer, Gregory Shimamura, Tetyana Kudlyk, Philip Jeffrey, Vladimir Lupashin, Frederick Hughson Publication Year 2014 Type Journal Article Abstract The conserved oligomeric Golgi (COG) complex is required, along with SNARE and Sec1/Munc18 (SM) proteins, for vesicle docking and fusion at the Golgi. COG, like other multisubunit tethering complexes (MTCs), is thought to function as a scaffold and/or chaperone to direct the assembly of productive SNARE complexes at the sites of membrane fusion. Reflecting this essential role, mutations in the COG complex can cause congenital disorders of glycosylation. A deeper understanding of COG function and dysfunction will likely depend on elucidating its molecular structure. Despite some progress toward this goal, including EM studies of COG lobe A (subunits 1-4) and higher-resolution structures of portions of Cog2 and Cog4, the structures of COG's eight subunits and the principles governing their assembly are mostly unknown. Here, we report the crystal structure of a complex between two lobe B subunits, Cog5 and Cog7. The structure reveals that Cog5 is a member of the complexes associated with tethering containing helical rods (CATCHR) fold family, with homology to subunits of other MTCs including the Dsl1, exocyst, and Golgi-associated retrograde protein (GARP) complexes. The Cog5-Cog7 interaction is analyzed in relation to the Dsl1 complex, the only other CATCHR-family MTC for which subunit interactions have been characterized in detail. Biochemical and functional studies validate the physiological relevance of the observed Cog5-Cog7 interface, indicate that it is conserved from yeast to humans, and demonstrate that its disruption in human cells causes defects in trafficking and glycosylation. Keywords Humans, Crystallography, X-Ray, Multiprotein Complexes, Protein Structure, Secondary, Protein Structure, Quaternary, Adaptor Proteins, Vesicular Transport Journal Proc Natl Acad Sci U S A Volume 111 Issue 44 Pages 15762-7 Date Published 2014 Nov 04 ISSN Number 1091-6490 DOI 10.1073/pnas.1414829111 Alternate Journal Proc Natl Acad Sci U S A PMCID PMC4226102 PMID 25331899 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML