title: Cog5-Cog7 crystal structure reveals interactions essential for the function of a multisubunit tethering complex.
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.
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, NJ 08544;
authors.forename: Jun Yong
authors.initials: JY
authors.lastname: Ha
authors.affiliation: Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR 72205; and.
authors.forename: Irina D
authors.initials: ID
authors.lastname: Pokrovskaya
authors.affiliation: Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR 72205; and.
authors.forename: Leslie K
authors.initials: LK
authors.lastname: Climer
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, NJ 08544;
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Shimamura
authors.affiliation: Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR 72205; and.
authors.forename: Tetyana
authors.initials: T
authors.lastname: Kudlyk
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, NJ 08544;
authors.forename: Philip D
authors.initials: PD
authors.lastname: Jeffrey
authors.affiliation: Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR 72205; and Biological Institute, Tomsk State University, Tomsk, 634050, Russian Federation.
authors.forename: Vladimir V
authors.initials: VV
authors.lastname: Lupashin
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, NJ 08544; hughson@princeton.edu.
authors.forename: Frederick M
authors.initials: FM
authors.lastname: Hughson
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018360:Crystallography, X-Ray; D006801:Humans; D046912:Multiprotein Complexes / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; C115632:COG5 protein, human; C512294:COG7 protein, human; D046912:Multiprotein Complexes
keywords: CATCHR; COG complex; Golgi; congenital glycosylation disorder; vesicle fusion