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

Abstract

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.

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