Structural basis for cargo regulation of COPII coat assembly

Cell. 2008 Aug 8;134(3):474-84. doi: 10.1016/j.cell.2008.06.024.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism
  • Cryoelectron Microscopy
  • Endoplasmic Reticulum / chemistry*
  • Endoplasmic Reticulum / metabolism*
  • Humans
  • Models, Molecular
  • Protein Transport
  • Vesicular Transport Proteins / chemistry*
  • Vesicular Transport Proteins / metabolism*

Substances

  • Carrier Proteins
  • SEC13 protein, human
  • SEC23A protein, human
  • SEC24C protein, human
  • SEC31A protein, human
  • Vesicular Transport Proteins