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Published June 22, 2010 | Published + Supplemental Material
Journal Article Open

Crystal structure of α-COP in complex with ϵ-COP provides insight into the architecture of the COPI vesicular coat


The heptameric coatomer complex forms the protein shell of membrane-bound vesicles that are involved in transport from the Golgi to the endoplasmatic reticulum and in intraGolgi trafficking. The heptamer can be dissected into a heterotetrameric F-subcomplex, which displays similarities to the adapter complex of the "inner" coat in clathrin-coated vesicles, and a heterotrimeric B-subcomplex, which is believed to form an "outer" coat with a morphology distinct from that of clathrin-coated vesicles. We have determined the crystal structure of the complex between the C-terminal domain (CTD) of α-COP and full-length ϵ-COP, two components of the B-subcomplex, at a 2.9 Å resolution. The α-COP^(CTD)•ϵ-COP heterodimer forms a rod-shaped structure, in which ϵ-COP adopts a tetratricopeptide repeat (TPR) fold that deviates substantially from the canonical superhelical conformation. The α-COP CTD adopts a U-shaped architecture that complements the TPR fold of ϵ-COP. The ϵ-COP TPRs form a circular bracelet that wraps around a protruding β-hairpin of the α-COP CTD, thus interlocking the two proteins. The α-COP^(CTD)•ϵ-COP complex forms heterodimers in solution, and we demonstrate biochemically that the heterodimer directly interacts with the Dsl1 tethering complex. These data suggest that the heterodimer is exposed on COPI vesicles, while the remaining part of the B-subcomplex oligomerizes underneath into a cage.

Additional Information

© 2010 National Academy of Sciences. Communicated by Günter Blobel, The Rockefeller University, New York, NY, May 10, 2010 (received for review April 5, 2010) We thank Andrew Davenport, Erik Debler, Jana Mitchell, Johanna Napetschnig, Alina Patke, Pete Stavropoulos, and Hyuk-Soo Seo for critical reading of the manuscript, Stephanie Etherton for help with editing the manuscript, Hans Schmitt for providing the Dsl1 peptide expression construct, and Günter Blobel for continuing support. In addition, we thank Erik Debler for help and Nagarajan Venugopalan (GM/CA-CAT) for support during data collection. Analytical ultracentrifugation was carried out by the Wadsworth Center Biochemistry Core Facility. A.H. was supported by a grant from the Leukemia and Lymphoma Society. Author contributions: K.-C.H. and A.H. designed research; performed research; contributed new reagents/analytic tools; analyzed data; and wrote the paper. The authors declare no conflict of interest. Data deposition: The atomic coordinates have been deposited in the Protein Data Bank, www.pdb.org (PDB ID codes 3MV2 and 3MV3). This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1006297107/-/DCSupplemental.

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Supplemental Material - pnas.1006297107_SI.pdf


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August 22, 2023
October 20, 2023