| Structural highlights
Function
SEC12_YEAST Guanine nucleotide-exchange factor (GEF) required for the formation or budding of transport vesicles from the ER. This function involves the cytoplasmic domain of the protein, which is thought to interact with the small GTP-binding protein SAR1. Required for autophagy.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16]
Publication Abstract from PubMed
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.
Structural basis for the initiation of COPII vesicle biogenesis.,Joiner AMN, Fromme JC Structure. 2021 Aug 5;29(8):859-872.e6. doi: 10.1016/j.str.2021.03.013. Epub 2021 , Apr 7. PMID:33831355[17]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
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- ↑ Campbell JL, Schekman R. Selective packaging of cargo molecules into endoplasmic reticulum-derived COPII vesicles. Proc Natl Acad Sci U S A. 1997 Feb 4;94(3):837-42. PMID:9023343
- ↑ Joiner AMN, Fromme JC. Structural basis for the initiation of COPII vesicle biogenesis. Structure. 2021 Aug 5;29(8):859-872.e6. PMID:33831355 doi:10.1016/j.str.2021.03.013
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