6X90

Structure of the guanine nucleotide exchange factor Sec12 bound to the small GTPase Sar1

Summary for 6X90

• Entry DOI: 10.2210/pdb6x90/pdb
• Descriptor: Guanine nucleotide-exchange factor SEC12, Small COPII coat GTPase SAR1, POTASSIUM ION, ... (4 entities in total)
• Functional Keywords: endoplasmic reticulum, gtpase, exchange factor, membrane trafficking, protein transport
• Biological source: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast); More
• Total number of polymer chains: 2
• Total formula weight: 59005.10

Authors

Joiner, A.M.N.,Fromme, J.C. (deposition date: 2020-06-02, release date: 2021-03-24, Last modification date: 2023-10-18)

Primary citation

Joiner, A.M.N.,Fromme, J.C.
Structural basis for the initiation of COPII vesicle biogenesis.
Structure, 29:859-872.e6, 2021

PubMed 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 orientation of the GEF domain relative to the membrane surface and postulate a mechanism for how Sec12 facilitates membrane insertion of the amphipathic helix exposed by Sar1 upon GTP binding.

PubMed: 33831355
DOI: 10.1016/j.str.2021.03.013

Experimental method

X-RAY DIFFRACTION (2.26 Å)