title: Structural basis for cargo regulation of COPII coat assembly.
abstract: Using cryo-electron microscopy, we have solved the structure of an icosidodecahedral COPII coat involved in cargo export from the endoplasmic reticulum (ER) coassembled 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 well 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 beta-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 is sensitive to adaptor function in inherited disease. The COPII coat structure leads us to propose a mechanism by which cargo drives cage assembly and membrane curvature for budding from the ER.
authors.affiliation: National Resource for Automated Molecular Microscopy, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Stagg
authors.forename: Paul
authors.initials: P
authors.lastname: LaPointe
authors.forename: Abbas
authors.initials: A
authors.lastname: Razvi
authors.forename: Cemal
authors.initials: C
authors.lastname: Gürkan
authors.forename: Clinton S
authors.initials: CS
authors.lastname: Potter
authors.forename: Bridget
authors.initials: B
authors.lastname: Carragher
authors.forename: William E
authors.initials: WE
authors.lastname: Balch
mesh_terms: D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism; D020285:Cryoelectron Microscopy; D004721:Endoplasmic Reticulum / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D021381:Protein Transport; D033921:Vesicular Transport Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; C507456:SEC13 protein, human; C512739:SEC23A protein, human; C530640:SEC24C protein, human; C507455:SEC31A protein, human; D033921:Vesicular Transport Proteins