8phv
From Proteopedia
(Difference between revisions)
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| - | ==Structure of Human Cdc123 | + | ==Structure of Human selenomethionylated Cdc123 bound to domain 3 of eIF2 gamma== |
<StructureSection load='8phv' size='340' side='right'caption='[[8phv]], [[Resolution|resolution]] 1.97Å' scene=''> | <StructureSection load='8phv' size='340' side='right'caption='[[8phv]], [[Resolution|resolution]] 1.97Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
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</table> | </table> | ||
== Function == | == Function == | ||
| - | [https://www.uniprot.org/uniprot/CD123_HUMAN CD123_HUMAN] | + | [https://www.uniprot.org/uniprot/CD123_HUMAN 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]<ref>PMID:35031321</ref> <ref>PMID:37507029</ref> |
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == 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. | 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 | + | 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<ref>PMID:37507029</ref> |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
Current revision
Structure of Human selenomethionylated Cdc123 bound to domain 3 of eIF2 gamma
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