Structural highlights
Function
CD123_HUMAN ATP-dependent protein-folding chaperone for the eIF2 complex (PubMed:35031321, PubMed:37507029). Binds to the gamma subunit of the eIF2 complex which allows the subunit to assemble with the alpha and beta subunits (By similarity).[UniProtKB:Q05791][1] [2]
Publication Abstract from PubMed
Eukaryotic initiation factor 2 (eIF2) plays a key role in protein synthesis and in its regulation. The assembly of this heterotrimeric factor is facilitated by Cdc123, a member of the ATP grasp family that binds the gamma subunit of eIF2. Notably, some mutations related to MEHMO syndrome, an X-linked intellectual disability, affect Cdc123-mediated eIF2 assembly. The mechanism of action of Cdc123 is unclear and structural information for the human protein is awaited. Here, the crystallographic structure of human Cdc123 (Hs-Cdc123) bound to domain 3 of human eIF2gamma (Hs-eIF2gammaD3) was determined. The structure shows that the domain 3 of eIF2gamma is bound to domain 1 of Cdc123. In addition, the long C-terminal region of Hs-Cdc123 provides a link between the ATP and Hs-eIF2gammaD3 binding sites. A thermal shift assay shows that ATP is tightly bound to Cdc123 whereas the affinity of ADP is much smaller. Yeast cell viability experiments, western blot analysis and two-hybrid assays show that ATP is important for the function of Hs-Cdc123 in eIF2 assembly. These data and recent findings allow us to propose a refined model to explain the mechanism of action of Cdc123 in eIF2 assembly.
Binding of human Cdc123 to eIF2gamma.,Cardenal Peralta C, Vandroux P, Neumann-Arnold L, Panvert M, Fagart J, Seufert W, Mechulam Y, Schmitt E J Struct Biol. 2023 Sep;215(3):108006. doi: 10.1016/j.jsb.2023.108006. Epub 2023 , Jul 27. PMID:37507029[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Vanselow S, Neumann-Arnold L, Wojciech-Moock F, Seufert W. Stepwise assembly of the eukaryotic translation initiation factor 2 complex. J Biol Chem. 2022 Feb;298(2):101583. PMID:35031321 doi:10.1016/j.jbc.2022.101583
- ↑ Cardenal Peralta C, Vandroux P, Neumann-Arnold L, Panvert M, Fagart J, Seufert W, Mechulam Y, Schmitt E. Binding of human Cdc123 to eIF2γ. J Struct Biol. 2023 Jul 27;215(3):108006. PMID:37507029 doi:10.1016/j.jsb.2023.108006
- ↑ Cardenal Peralta C, Vandroux P, Neumann-Arnold L, Panvert M, Fagart J, Seufert W, Mechulam Y, Schmitt E. Binding of human Cdc123 to eIF2γ. J Struct Biol. 2023 Jul 27;215(3):108006. PMID:37507029 doi:10.1016/j.jsb.2023.108006
