@article{86926,
  keywords = {Crystallography, X-Ray, Humans, Multiprotein Complexes, Protein Structure, Secondary, Protein Structure, Quaternary, Adaptor Proteins, Vesicular Transport},
  author = {Jun Yong Ha and Irina Pokrovskaya and Leslie Climer and Gregory Shimamura and Tetyana Kudlyk and Philip Jeffrey and Vladimir Lupashin and Frederick Hughson},
  title = {Cog5-Cog7 crystal structure reveals interactions essential for the function of a multisubunit tethering complex.},
  abstract = {<p>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{\textquoteright}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.</p>
},
  year = {2014},
  journal = {Proc Natl Acad Sci U S A},
  volume = {111},
  pages = {15762-7},
  month = {10/2014},
  issn = {1091-6490},
  doi = {10.1073/pnas.1414829111},
  language = {eng},
}