Structural Basis for Cargo Regulation of COPII Coat Assembly

Abstract

SUMMARY Using cryo-electron microscopy, we have solved the structure of a novel icosidodecahedral COPII coat involved in cargo export from the endoplasmic reticulum (ER) co-assembled from purified cargo adaptor Sec23–24 and Sec13–31 lattice forming complexes. The coat structure shows a tetrameric assembly of the Sec23–24 adaptor layer that is positioned beneath the vertices and edges of the Sec13–31 lattice. Fitting the known crystal structures of the COPII proteins into the density map reveals a flexible hinge region stemming from interactions between WD40 β-propeller domains present in Sec13 and Sec31 at the vertices. The structure shows that the hinge region can direct geometric cage expansion to accommodate a wide range of bulky cargo including procollagen and chylomicrons that are sensitive to adaptor function in inherited disease. The COPII coat structure leads us to propose a new mechanism by which cargo drives cage assembly and membrane curvature for budding from the ER.

ArfGAP1 promotes COPI vesicle formation by facilitating coatomer polymerization

“…49,50 COPII has also been found to assemble independent of membrane binding. [51][52][53] The function of ArfGAP1 to facilitate assembly of COPI independent of membranes is analogous to that of clathrin adaptors AP-1 and AP-2 and the catalytic function is analogous to that of Sec23 in COPII, which is thought to be analogous to clathrin adaptors. [54][55][56][57] Thus, our results are consistent with previous work identifying ArfGAP1 as a coat component.…”

Mea6 controls VLDL transport through the coordinated regulation of COPII assembly

“…The outer coat subunit of COPII, Sec31A, interacts with the inner coat subunits, Sec23A and Sec24D [35]. We have shown above that Mea6 interacts with Sec23A and Sec24D, which interact with each other [35] (Supplementary information, Figure S5C), but it did not interact with Sec13 or Sec31A ( Figure 7A, Supplementary information, Figure S5B).…”

“…We have shown above that Mea6 interacts with Sec23A and Sec24D, which interact with each other [35] (Supplementary information, Figure S5C), but it did not interact with Sec13 or Sec31A ( Figure 7A, Supplementary information, Figure S5B). We therefore hypothesized that Mea6 might interact with Sec13 and Sec31A via Sec23A or Sec24D (model in Figure 7B).…”

Régulation du transport vésiculaire par la courbure membranaire

“…Soixante d'entre eux vont s'assembler en une cage icosidodécaédrique, dont chaque sommet est positionné au-dessus de quatre hétérodimères Sec23/24 qui servent donc de piliers à cet assemblage. La formation de la cage va unifier les points de courbure générés par les complexes Sar1-Sec23/24 [11] et donc induire une déformation globale de la membrane en un bourgeon (Figure 2). responsables de chacune de ces étapes, en particulier pour comprendre comment les protéines du manteau engendrent ou reconnaissent des déformations de la membrane.…”