Structure of the complete, membrane-assembled COPII coat reveals a complex interaction network

Abstract

SummaryThe COPII coat mediates Endoplasmic Reticulum (ER) to Golgi trafficking of thousands of proteins. Five essential coat components assemble on the ER membrane to induce the formation of transport vesicles while selectively recruiting cargo proteins. Individual COPII proteins interact dynamically through multiple interfaces to assemble into inner and outer coat layers, forming coats of varied architectures. Here we have used cryo-electron tomography (cryo-ET) and subtomogram averaging to visualise the complete membrane-bound COPII coat to unprecedented detail, revealing a complex interaction network that includes a number of previously unknown interfaces. We identify essential interactions, and functionally characterise their contribution to COPII assembly and membrane remodelling. We find that multiple finely-tuned interfaces contribute to coat organization required to remodel membranes, depending additionally on membrane properties. Our work sheds light on how COPII transports the diverse range of cargo molecules required by the cell.

Combinatorial multivalent interactions drive cooperative assembly of the COPII coat

“…We propose that charge-driven interactions between Sec23 and Sec31 represent a novel third binding mode that contributes to inner/outer coat interactions. Indeed, recent structural analysis reveals that this region of Sec23 participates in a protein–protein interaction in the context of the fully assembled coat, consistent with our proposal that positively charged regions of Sec31 engage this site ( Hutchings et al, 2020 Preprint ).…”