Structural basis for the initiation of COPII vesicle biogenesis.

ABSTRACT: The first stage of the eukaryotic secretory pathway is the packaging of cargo proteins into coat protein complex II (COPII) vesicles exiting the ER. The cytoplasmic COPII vesicle coat machinery is recruited to the ER membrane by the activated, GTP-bound, form of the conserved Sar1 GTPase. Activation of Sar1 on the surface of the ER by Sec12, a membrane-anchored GEF (guanine nucleotide exchange factor), is therefore the initiating step of the secretory pathway. Here we report the structure of the complex between Sar1 and the cytoplasmic GEF domain of Sec12, both from Saccharomyces cerevisiae. This structure, representing a key nucleotide-free activation intermediate, reveals how the potassium ion-binding K loop disrupts the nucleotide-binding site of Sar1. We propose an unexpected orientati

SUBMITTER: Joiner AMN 

PROVIDER: S-EPMC8349879 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature